Active ingredients: Ceftriaxone (Ceftriaxone sodium)
Rocefin 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use
Rocefin 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
Rocefin package inserts are available for pack sizes: - Rocefin 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use, Rocefin 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
- Rocefin 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use
- Rocefin 1 g / 10 ml powder and solvent for solution for injection for intravenous use
- Rocefin 2 g powder for solution for infusion
Indications Why is Rocefin used? What is it for?
Rocefin contains the active substance ceftriaxone which is an antibiotic that is given to adults and children (including infants). It works by killing the bacteria that cause infections. It belongs to a group of medicines called cephalosporins.
Rocefin 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 Rocefin should not be used
You must not be given Rocefin if:
- you are allergic to ceftriaxone or any of the other ingredients of this medicine
- 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 Rocefin must be given to you by injection into a muscle.
Rocefin must 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 you take Rocefin
Talk to your doctor, pharmacist or nurse before you are given Rocefin 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.
Children
Talk to your doctor, pharmacist or nurse before giving your child Rocefin if:
- the child has recently received or is about to receive a product that contains calcium through a vein.
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 that Rocefin treatment would bring you and the possible risks to your baby.
Driving and using machines
Rocefin can cause dizziness. If you feel dizzy, do not drive or use any tools or machines. Contact your doctor if you experience these symptoms.
Interactions Which drugs or foods can modify the effect of Rocefin
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:
If you are due to have a blood or urine test
If you are given Rocefin for a long time, you may need to have regular blood tests. Rocefin 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 Rocefin has been given to you.
Dose, Method and Time of Administration How to use Rocefin: Posology
Rocefin is usually given by a doctor or nurse as an injection given directly into a muscle. Rocefin 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 Rocefin 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 Rocefin 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 Rocefin 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 Rocefin once daily for each kg of the infant'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 Rocefin 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 too much Rocefin
If you are accidentally given more Rocefin than your prescribed dose, contact your doctor or the nearest hospital immediately.
If you forget to take Rocefin
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 Rocefin
Do not stop taking Rocefin 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 Rocefin
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 Rocefin 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 (Kernittero).
- 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).
- Rocefin 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
Expiry: see the expiry date indicated on the package.
Warning: do not use the medicine after the expiry date indicated on the package. The expiry date indicated refers to the product in intact packaging, correctly stored.
Do not store above 30 ° C. Keep the vial in the original container. Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Disposal of syringes / stinging objects
The following list of points must be strictly observed regarding the use and disposal of syringes and other stinging medical devices:
- Needles and syringes must never be reused.
- Place all used needles and syringes in a special container for stinging objects (disposable puncture-proof container).
- Keep the container out of the reach of children.
- Containers for used stinging objects should not be placed in household waste.
- Dispose of the full container according to local requirements or as directed by your doctor.
Disposal of expired / unused drugs
The release of drugs into the environment should be minimized. Medicines should not be disposed of via wastewater or household waste. Use dedicated collection systems, if available.
What Rocefin contains
Rocefin 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; one solvent vial contains: 1% aqueous solution of lidocaine.
Rocefin 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.
Description of what Rocefin looks like and contents of the pack
Rocefin 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
1 vial of powder + 1 vial of 2 ml solvent.
Rocefin 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
ROCEFIN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Rocefin 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.
Rocefin 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.
Rocefin 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
One vial of powder contains:
Active ingredient: disodium ceftriaxone 3.5 H2O 1.193 g equal to ceftriaxone 1 g.
Rocefin 1 g / 10 ml powder and solvent for solution for injection for intravenous use
One vial of powder contains:
Active ingredient: disodium ceftriaxone 3.5 H2O 1.193 g equal to ceftriaxone 1 g.
Rocefin 2 g powder for solution for infusion
One vial contains:
Active ingredient: disodium ceftriaxone 3.5 H2O 2.386 g equal to ceftriaxone 2 g.
For the full list of excipients, see section 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 defunct 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 1 g of Rocefin 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 enzyme 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 Rocefin should be continued for a minimum of 48-72 hours after febrile 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: 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
The reconstituted solutions retain their physico-chemical characteristics for 6 hours at room temperature (or for 24 hours at + 5 ° C). As a general rule, however, the solutions should be used immediately after preparation.
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
For intramuscular injection, dissolve Rocefin im with the appropriate solvent (1% lidocaine solution) which is 2 ml for Rocefin 250 mg and 500 mg, and 3.5 ml for Rocefin 1 g: deeply inject the solution impromptu thus obtained in the buttock, alternating the buttocks in subsequent injections.
The lidocaine solution should not be administered intravenously.
Solution for intravenous use
To perform the i.v. injection, dissolve Rocefin with the appropriate solvent (water for injections) which is 10 ml for Rocefin 1 g, and inject directly into a vein in 2-4 minutes.
Solution for infusion
To carry out intravenous perfusion, dissolve Rocefin 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 6%, solutions of NaCl 0.45% + glucose 2.5%).
The perfusion will last for at least 30 minutes.
Rocefin 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
Rocefin is contraindicated in patients with known hypersensitivity to beta-lactam antibiotics.
Hypersensitivity to cephalosporins or to any of the excipients. In case of hypersensitivity to penicillins, the possible onset of cross allergy should be taken into account. 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. Education 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 full-term infants (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 newborns (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 using lidocaine as a solvent, 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 reactions with fatal outcome have been reported, including in patients with unknown allergy or previous exposure.
Each gram of Rocefin contains 3.6x mmol of sodium. This should be taken into consideration in patients on a controlled sodium diet.
Immune-mediated haemolytic anemia has been observed in patients receiving cephalosporin class antibacterials, including Rocefin. Severe cases of haemolytic anemia, including fatal cases, have been reported during treatment in both adults and children. If a patient develops anemia during treatment. ceftriaxone treatment, the diagnosis of cephalosporin-associated anemia should be considered and ceftriaxone treatment discontinued until etiology is determined.
As with almost all antibacterial drugs, including Rocefin, cases of associated diarrhea have been reported Clostridium difficile (CDAD), the severity of which can range from mild diarrhea to fatal colitis. Treatment with antibacterials alters the normal flora of the colon and leads to an overgrowth ofC. hard.
The C. difficile produces toxins A and B which contribute to the development of CDAD. The strains of C. difficile that produce excess toxins cause increased morbidity and mortality rates as these infections may be refractory to antimicrobial therapy and may require colectomy. The possibility of CDAD should be considered in all patients who present with diarrhea following antibiotic treatment. A careful medical history is also required since cases of CDAD have been reported even more than two months after the administration of antibacterials.
In case of suspected or overt CDAD, it may be necessary to stop the antibiotic treatment in progress, not aimed at C. hard. If clinically indicated, appropriate fluid and electrolyte management, protein supplementation, and antibiotic treatment measures should be instituted. C. hard; a surgical evaluation must also be performed.
As with other antibacterials, superinfections with non-sensitive microorganisms can occur.
Shadows, often confused with gallstones, have been observed in biliary ultrasound scans, usually after administration of higher than standard recommended doses. These shadows are, however, precipitates of calcium-ceftriaxone which disappear upon termination or discontinuation of Rocefin therapy. Rarely, these findings were associated with symptoms. In symptomatic cases, conservative non-surgical management is recommended; Stopping treatment with Rocefin should be at the physician's discretion.
Approximately 56% of Rocefin is eliminated in the urine and 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 situation, a reduction of the Rocefin 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, ceftriaxone has been shown to 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, ultrasonography 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 initiating therapy with Rocefin, a thorough investigation should be carried out to establish whether the patient has experienced hypersensitivity to cephalosporins, penicillins and other drugs in the past.
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 Rocefin higher than 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. Rocefin therapy 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 Rocefin 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 due to the presence of calcium precipitates in the lung and kidney in premature and full-term infants less than 1 month of age have been reported. At least one of these infants had been given ceftriaxone and calcium at different times and through different infusion routes. From the scientific data available at the moment, there are no cases 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 have shown that infants have a higher risk of ceftriaxone-calcium precipitate formation than other age groups.
However, ceftriaxone should not be mixed or administered simultaneously with calcium-containing solutions for intravenous administration. in patients of any age, even if for 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 if infusion lines are used at different sites or if the infusion lines are replaced or if they are thoroughly flushed with physiological saline between the two infusions to avoid precipitation. In patients requiring continuous infusion of TNP solutions of calcium salts, healthcare professionals may need to consider using an alternative antibacterial that is free of this precipitation risk. If the use of ceftriaxone is considered necessary in patients requiring continuous nutrition, the TNP solution and ceftriaxone can be administered simultaneously, albeit through different infusion lines at different sites. Alternatively, the infusion of the TNP solutions should be stopped during the infusion of ceftriaxone, taking into consideration the advice to flush the infusion lines between the administration of the two solutions (see sections 4.3, 4.8, 5.2 and 6.2).
Cases of pancreatitis, potentially secondary to biliary obstruction, have been reported rarely among patients treated with Rocefin. Most of the patients had risk factors for biliary stasis and biliary sludge, such as major therapy, severe disease, or prior total parenteral nutrition. It cannot be excluded that Rocefin acts as a trigger or co-factor in biliary precipitation.
In cases of severe renal and hepatic insufficiency it is necessary to reduce the dosage according to the established recommendations.
The safety and efficacy of Rocefin in neonates, infants and children have been established for the dosages reported in the Posology and method of administration sections. Some studies have shown that ceftriaxone, like other cephalosporins, can displace bilirubin from its serum albumin binding sites.
Rocefin must not be given to neonates (particularly premature babies) at risk of developing bilirubin encephalopathy.
During prolonged treatment, complete blood cell counts should be performed at regular intervals.
In case lidocaine is used as a solvent, Ceftriaxone solutions should only be used for intramuscular injection.
04.5 Interactions with other medicinal products and other forms of interaction
The concomitant administration of high doses of Rocefin with high-activity diuretics (eg furosemide) at high doses has not shown up to now disturbances in renal function. There is no evidence that Rocefin increases the renal toxicity of aminoglycosides. Ingestion of alcohol following administration of Rocefin 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. The elimination of Rocefin is not modified by probenecid.
In a studio in vitro antagonistic effects were observed with the combination of chloramphenicol and ceftriaxone.
It has been demonstrated in experimental conditions synergism of action between Rocefin 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 others. treatments, due to organisms such as Pseudomonas aeruginosa. Due to physical incompatibilities, the two drugs must be administered separately at the recommended doses.
Rocefin must not be added to solutions that contain calcium, such as Hartmann and Ringer solutions (see sections 4.3, 4.4 and 4.8).
Calcium-containing diluents, such as Ringer's or Hartmann's solution, should not be used to reconstitute vials of Rocefin or to further dilute reconstituted vials for i.v. administration, as a precipitate may form.Precipitation of ceftriaxone-calcium can also occur when Rocefin is mixed with calcium-containing solutions in the same IV administration line. Rocefin must not be administered simultaneously with i.v. solutions. containing calcium, including continuous calcium-containing infusions such as those for parenteral nutrition administered via a system with a common end-tract (Y-connector). However, in non-neonatal patients, Rocefin and calcium-containing solutions can be administered sequentially as long as the infusion lines are thoroughly flushed with a compatible liquid between infusions. Education in vitro conducted on plasma from adult and neonatal patients, derived from umbilical cord blood, have shown that neonates have an increased risk of precipitation of ceftriaxone-calcium.
Based on literature data, ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole and aminoglycosides.
The Coombs test may rarely give false positive results in patients treated with Rocefin.
Rocefin, like other antibiotics, can lead to false positive test results for galactosemia.
Similarly, non-enzymatic methods for the determination of glycosuria can give false-positive results. For this reason, the determination of glucose in the urine during Rocefin therapy should be performed by enzymatic methods.
Ceftriaxone may impair the efficacy of hormonal oral contraceptives. Therefore, it is advisable to use additional non-hormonal contraceptive measures during treatment and for the following month.
04.6 Pregnancy and lactation
Ceftriaxone crosses the placental barrier. Safety in humans during pregnancy has not been established. Reproduction studies in animals have shown no evidence of embryotoxicity, foetotoxicity, teratogenicity or adverse effects on male or female fertility, birth or perinatal and postnatal development. primates, no embryotoxicity or teratogenicity was observed. Ceftriaxone is excreted in low concentrations in breast milk. Care should be taken when prescribing Rocefin to breastfeeding women. In pregnant, lactating and very early infancy women, the product it 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 Rocefin sometimes induces dizziness, the ability to drive and use machines may be impaired.
04.8 Undesirable effects
Side effects are usually mild and short-term.
Systemic side effects
Gastrointestinal disorders (about 2% of cases): loose stools, diarrhea, nausea, vomiting, stomatitis, glossitis, rarely thickening of the bile.
Hematological changes (about 2%): eosinophilia, leukopenia, granulocytopenia, haemolytic anemia, thrombocytopenia. Frequency not known: Cases of agranulocytosis have been reported, most after 10 days of treatment and after total doses of 20 grams or more.
Skin reactions (approximately 1%): rash, allergic dermatitis, pruritus, urticaria and edema. Frequency not known: cases of severe skin adverse reactions (erythema multiforme, Stevens Johnson syndrome or Lyell's syndrome / toxic epidermal necrolysis have been reported ).
Other rare side effects: headache, dizziness, precipitation of ceftriaxone-calcium salts in the gallbladder, increased transaminases, glycosuria, haematuria, oliguria, increased serum creatinine, mycosis of the genital tract, chills, fever and anaphylactic or anaphylactoid reactions, for example bronchospasm.
The occurrence of anaphylactic shock is extremely rare and requires immediate countermeasures such as intravenous administration of adrenaline followed by a glucocorticoid.
Rare cases of pseudomembranous enterocolitis and changes in blood coagulation parameters have been reported following the use of cephalosporins. There have been reports of haemolytic anemia following treatment with cephalosporins. Rocefin must not be mixed or administered simultaneously with calcium-containing solutions or products. , even if infused separately.
Rare, serious, and in some cases fatal adverse reactions have been reported in preterm and full-term infants (age
The presence of ceftriaxone precipitates and calcium salts in the lung and kidney was also verified post-mortem.
The high risk of precipitation in neonates is due to their low blood volume and the long half-life of ceftriaxone when 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. Pseudomembranous colitis is a rare side effect caused by infection with Clostridium difficult during treatment with Rocefin. Therefore, the possibility of disease should be considered in patients presenting with diarrhea following antibacterial treatment.
Very rare cases of renal precipitation have been reported, predominantly in children over 3 years of age, treated with high daily doses (e.g., ≥ 80 mg / kg / day) or with total doses greater than 10 grams and who had other factors risk (for example, limited fluid intake, bed rest, etc.). The risk of precipitate formation is greater in immobilized or dehydrated patients. This event can be symptomatic or asymptomatic, can lead to renal failure and anuria, and is reversible after stopping treatment with Rocefin.
Precipitation of ceftriaxone-calcium salts has been observed in the gallbladder, predominantly in patients treated with higher than standard recommended doses. In children, prospective studies have shown a "variable incidence of precipitation with intravenous administration, in some studies greater than 30%. The incidence appears to be lower with slow infusion (20-30 minutes). This effect is generally asymptomatic. , however, 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 precipitation is usually reversible after discontinuation of ceftriaxone treatment.
Isolated cases of pancreatitis have been reported.
Bleeding disorders have been reported as very rare side effects.
Local side effects
In rare cases, phlebitic reactions have appeared after i.v. administration; however, these reactions can be avoided by slow injection (2-4 minutes) of the drug.
Intramuscular injection without lidocaine is painful.
Hypersensitivity reactions may occur in predisposed subjects.
Influence on diagnostic tests
Rarely, the Coombs test may give false positive results in patients treated with Rocefin.
Rocefin, like other antibiotics, can lead to false positive test results for galactosemia.
Similarly, non-enzymatic methods of determining glycosuria can give false-positive results. For this reason, the determination of glucose in the urine during Rocefin therapy should be performed by enzymatic methods.
04.9 Overdose
In the event of an overdose, nausea, vomiting and diarrhea may occur. The concentration of ceftriaxone cannot be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Symptomatic treatment is indicated.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: beta-lactam 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 sections 4.1) due to the following Gram negative germs: Enterobacter, Serratia marcescens, Citrobacter, Pseudomonas aeruginosa. Ceftriaxone also shows good activity against anaerobic bacteria. This activity, together with 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 susceptibility of Gram-positive and Gram-negative pathogens to Rocefin can be assessed either by the diffusion test with discs or 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, renal excretion returns to levels similar to those in adults. In infants less than 8 days of age, the mean elimination half-life is generally two to three times longer than that of a young adult.
05.3 Preclinical safety data
Toxicological studies have shown an LD50 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 1% aqueous solution of lidocaine.
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 calcium-containing diluents (e.g. Ringer's or Hartmann's solutions), should not be used to reconstitute ceftriaxone vials or to further dilute reconstituted ceftriaxone vials for i.v. administration, as a precipitate may form. Ceftriaxone must not be mixed or administered simultaneously with calcium-containing solutions (see sections 4.2, 4.3, 4.4 and 4.8).
06.3 Period of validity
It is recommended to use freshly prepared Rocefin solutions even if the drug, once dissolved, is stable for 6 hours at room temperature and for 24 hours in the refrigerator.
06.4 Special precautions for storage
Store at a temperature not exceeding 30 ° C. Keep the vial in the original container.
06.5 Nature of the immediate packaging and contents of the package
Glass vial (plus any glass vial for reconstitution liquids) with pierceable rubber stopper, fixed with a metal ring, and plastic cap. The vial is enclosed in a cardboard box together with the package leaflet.
The vial of Rocefin 2 g is equipped with a label equipped with a plastic bracket designed to allow the vial to be hung on the normal supports for perfusional liquids.
Rocefin 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use
1 vial of powder + 1 vial of 2 ml solvent
Rocefin 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use
1 vial of powder + 1 vial of 2 ml solvent
Rocefin 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; 1 vial powder + 1 solvent vial of 3.5 ml + administration kit
Rocefin 1 g / 10 ml powder and solvent for solution for injection for intravenous use
1 vial of powder + 1 vial of 10 ml solvent
Rocefin 2 g powder for solution for infusion
1 vial
06.6 Instructions for use and handling
Disposal of syringes / stinging objects
The following list of points must be strictly observed regarding the use and disposal of syringes and other stinging medical devices:
• Needles and syringes must never be reused.
• Place all used needles and syringes in a special container for stinging objects (disposable, puncture-proof container).
• Keep the container out of the reach of children.
• Containers for used stinging objects should not be placed in household waste.
• Dispose of the full container according to local requirements or according to your doctor's instructions.
Disposal of expired / unused drugs
The release of drugs into the environment should be minimized. Medicines should not be disposed of via wastewater or household waste. Use dedicated collection systems, if available.
07.0 MARKETING AUTHORIZATION HOLDER
Roche S.p.A. - Piazza Durante 11 - 20131 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Rocefin 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use
1 powder vial + 1 2 ml solvent vial AIC n ° 025202019
Rocefin 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use
1 powder vial + 1 2 ml solvent vial AIC n ° 025202033
Rocefin 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 AIC n ° 025202058
1 vial powder + 1 solvent vial of 3.5 ml + AIC administration kit n ° 025202110
Rocefin 1 g / 10 ml powder and solvent for solution for injection for intravenous use
1 powder vial + 1 10 ml solvent vial AIC n ° 025202096
Rocefin 2 g powder for solution for infusion
1 vial AIC n ° 025202108
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal: June 2010
10.0 DATE OF REVISION OF THE TEXT
July 2010
