Active ingredients: Ceftriaxone
FIDATO 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use
FIDATO 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use
TRUST 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
TRUST 1 g / 10 ml powder and solvent for solution for injection for intravenous use
TRUST 2 g powder for solution for infusion
Why is Fidato used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antibiotic; beta-lactam antibacterial for systemic use.
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.
Contraindications When Trustworthy is not to be used
FIDATO 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. In vitro studies 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-ceftriaxone salts in full-term births.
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 may be impaired - if they require (or are thought to require) IV treatment. with calcium or with calcium-containing infusions due to the risk of precipitation of ceftriaxone with calcium (see Precautions for use, Side effects and Dose, method and time of administration).
When lidocaine is used as a diluent, contraindications related to lidocaine should be excluded prior to the intramuscular injection of ceftriaxone.
Precautions for use What you need to know before taking Fidato
As with other cephalosporins, anaphylactic shock cannot be excluded, even in the presence of an accurate patient history.
Each gram of FIDATO contains 3.6 x mmol of sodium. To be taken into consideration in patients on a low sodium diet. Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including FIDATO, and can range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters normal flora. difficult, causing overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing C. difficile strains cause increased morbidity and mortality as these infections can be refractory antimicrobial therapy and may require colectomy. CDAD should be considered in all patients who develop diarrhea following antibiotic use. A thorough 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 discontinue the use of antibiotics not directly in opposition to C. difficile. Depending on the clinical indications, adequate fluid and electrolyte management, protein supplementation, should be instituted. C. difficile antibiotic treatment 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 FIDATO therapy. These findings have rarely been associated with symptoms. In symptomatic cases, non-surgical conservative management is recommended. In symptomatic cases, discontinuation of treatment with FIDATO should be at the discretion of the physician.
Cases of fatal reactions with calcium-ceftriaxone precipitates in the lungs and kidneys in preterm and full-term newborns 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. In vitro studies have shown that neonates have an increased risk of calcium ceftriaxone precipitation compared to other age groups.
In patients of any age, FIDATO should not be mixed or administered simultaneously with any calcium-containing intravenous solution, even through 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, as long as infusion lines are used at different sites or if, between infusions, the infusion lines are replaced or thoroughly washed with a physiological saline solution to avoid precipitation. In patients requiring continuous infusion with calcium-containing TNP solutions, healthcare professionals may consider using alternative antibacterial treatments that do not carry a similar risk of precipitation. If the use of ceftriaxone is considered necessary in patients requiring continuous feeding, the solutions for TNP and ceftriaxone can be administered at the same time, provided that through different infusion lines and at different sites. Alternatively, the infusion of TNP solution can be stopped. for the period of infusion of ceftriaxone, observing the precaution of flushing the infusion lines between one administration and the other (see sections Contraindications, Undesirable effects and Dose, method and time of administration). Cases of pancreatitis, possibly due to biliary obstruction, have been observed rarely in patients treated with FIDATO. Most patients have 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 FIDATO-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 FIDATO in neonates, infants and children have been established for the dosages described in the Dosage and Administration section. Clinical studies have shown that ceftriaxone, like some other cephalosporins, can remove bilirubin from serum albumin. FIDATO should not be used in infants (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.
Before initiating therapy with FIDATO, a thorough investigation should be carried out to establish whether the patient has in the past exhibited phenomena of hypersensitivity to cephalosporins, penicillins and other drugs. The product should be administered with caution in patients allergic to penicillin as they are described cases of cross hypersensitivity between penicillins and cephalosporins. Due to the immaturity of the organ functions, premature babies should not be treated with doses of FIDATO higher than 50 mg / kg / day. As with other antibiotics, prolonged use can favor the development of resistant bacteria and in case of superinfection the most appropriate measures must be taken. 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 susceptibility testing, 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. The therapy with FIDATO can however be started pending the results of these analyzes; and treatment should still be, if necessary, subsequently modified according to the results of the analyzes.
Before using FIDATO in combination with other antibiotics, the instructions for use of the other drugs should be carefully re-read in order to know any contraindications, warnings, precautions and unwanted reactions. Renal function should be carefully monitored. Pseudomembranous colitis have 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 Which drugs or foods can modify the effect of Fidato
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The simultaneous administration of high doses of FIDATO with high activity diuretics (eg furosemide) at high doses has not shown up to now disturbances in renal function. There is no evidence that FIDATO increases the renal toxicity of aminoglycosides.The ingestion of alcohol following the administration of FIDATO 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 FIDATO is not modified by probenecid. In an in vitro study with the combination of chloramphenicol and ceftriaxone antagonistic effects were observed. Synergism of action between FIDATO and aminoglycosides against many Gram germs was demonstrated under experimental conditions. 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.
TRUSTED should not be added to solutions that contain calcium such as Hartmann and Ringer solutions. Do not use calcium-containing diluents, such as Ringer's Solution or Hartmann's Solution, to reconstruct TRUSTED vials or to further dilute a reconstructed vial for IV administration, as precipitate can form. Precipitation of calcium-ceftriaxone can also occur when FIDATO is mixed with calcium-containing solutions in the same IV administration line. FIDATO 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 non-neonatal patients, FIDATO and calcium-containing solutions can be administered sequentially, one after the other, as long as the lines are thoroughly flushed with a compatible liquid between infusions. In vitro studies performed. with adult plasma and neonate plasma from 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. cases in patients treated with FIDATO the Coombs test can produce false positives. FIDATO, like other antibiotics, can cause false positives in tests for galactosemia. Likewise, non-enzymatic methods for determining glucose in urine can produce false positive results. for this reason, the determination of glucose levels in the urine during therapy with FIDATO must eg be performed 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.
Warnings It is important to know that:
TRUST is eliminated for about 56% through the urine and the remaining 44% through 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 even in this circumstance the half-life is only slightly increased, in most cases it is not necessary to reduce the dosage of FIDATO, provided that the 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 combining more beta-lactamines. As with any antibiotic therapy, in case of prolonged treatments, regular checks of the blood crase should be carried out. In extremely rare cases, in patients treated with high doses, the "Ultrasound of the gallbladder revealed findings that could 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.
PREGNANCY AND BREASTFEEDING
Ask your doctor or pharmacist for advice before taking any medicine. Ceftriaxone crosses the placental barrier. Its safety during human pregnancy has not been established. Animal reproduction studies have shown no evidence of embryotoxicity, phototoxicity 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 administering FIDATO 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 direct medical supervision.
Effects on ability to drive and use machines
Because TRUST sometimes induces dizziness, the ability to drive and use machines may be impaired.
Dosage and method of use How to use Fidato: Dosage
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 IV 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 Contraindications, Precautions for use and Undesirable effects).
General dosage schedule
Adults and children over 12 years: the recommended dose is 1g of FIDATO 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.
Newborns (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 "Special warnings").
Children (from 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.
Elderly: the dosage regimen for adults does not require modification in the case of elderly patients. The duration of the therapy depends on the course of the infection. Like all antibiotic-based therapies, in general the administration of FIDATO 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
Renal insufficiency: 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 posology.
Associated renal and hepatic insufficiency: check plasma concentrations of ceftriaxone.
Premature babies: maximum dose 50 mg / kg once a day.
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 practice the intramuscular injection, dissolve FIDATO im with the special solvent (1% lidocaine solution) which is 2 ml for FIDATO 250 mg and 500 mg, and 3.5 ml for FIDATO 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 practice the IV injection, dissolve FIDATO with the special solvent (water for injections) which is 10 ml per FIDATO 1 g, and inject directly into a vein in 2-4 minutes.
Solution for infusion
To carry out intravenous perfusion, dissolve FIDATO 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%,). The perfusion will last for at least 30 minutes. FIDATO solutions should not be mixed in solutions containing other antimicrobial drugs or with diluting solutions other than those listed above due to possible incompatibility.
Overdose What to do if you have taken an overdose of Fidato
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. In case of accidental intake of an overdose of FIDATO, notify your doctor immediately or go to the nearest hospital.
IF YOU HAVE ANY DOUBT ABOUT USING TRUSTED, ASK YOUR DOCTOR OR PHARMACIST
Side Effects What are the side effects of Fidato
Like all medicines, FIDATO can cause side effects, although not everybody gets them.
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: No cases of agranulocytosis (<500 / mm3) have been reported, most of which 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. The occurrence of anaphylactic shock is extremely rare and requires immediate countermeasures such as intravenous administration of adrenaline followed by a glucocorticoid. 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 (age <28 days) who were treated with intravenous ceftriaxone and calcium.
In the lungs and kidneys, precipitation of calcium ceftriaxone salt has been observed post mortem. 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 Contraindications and Special Warnings).
Superinfections caused by microorganisms not sensitive to ceftriaxone (candida, fungi or other resistant microorganisms) may develop. A rare side effect caused by Clostridium difficile infection during treatment with FIDATO is pseudomembranous colitis. Therefore, in patients who present with diarrhea following the use of a bacterial agent, the possibility of developing this disease should be considered. 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 had high risk factors (e.g. fluid restrictions, confinement to bed, etc.). The risk of precipitate formation increases in dehydrated or immobilized patients. This event can be symptomatic or asymptomatic, can cause renal failure and anuria and is reversible on discontinuation of FIDATO.
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).
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 FIDATO. Like other antibiotics, FIDATO can produce 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 FIDATO therapy must be carried out enzymatically.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
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.
For the reconstituted solution see "Method of administration".
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.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN
Composition and pharmaceutical form
COMPOSITION
FIDATO 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use
A bottle 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.
FIDATO 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; one solvent vial contains: 1% aqueous solution of lidocaine.
TRUST 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
A bottle of powder contains: active ingredient: ceftriaxone disodium 3.5 H2O 1.193 g equal to ceftriaxone 1g; one solvent vial contains: 1% aqueous solution of lidocaine.
TRUST 1 g / 10 ml powder and solvent for solution for injection for intravenous use
A bottle of powder contains: active ingredient: ceftriaxone disodium 3.5 H2O 1.193 g equal to ceftriaxone 1g; one solvent ampoule contains: water for injection.
TRUST 2 g powder for solution for infusion
One bottle contains: active ingredient: ceftriaxone disodium 3.5 H2O 2.386 g equal to ceftriaxone 2 g.
PHARMACEUTICAL FORM AND CONTENT
FIDATO 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use: 1 bottle of powder + 1 solvent ampoule of 2 ml.
FIDATO 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use: 1 bottle of powder + 1 vial of 2 ml solvent.
TRUST 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use: 1 bottle of powder + 1 vial of 3.5 ml solvent.
TRUST 1 g / 10 ml powder and solvent for solution for injection for intravenous use: 1 bottle of powder + 1 vial of 10 ml solvent.
TRUST 2 g powder for solution for infusion: 1 bottle of powder.
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
TRUSTWORTHY
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
FIDATO 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use
• a bottle of powder contains:
active principle: ceftriaxone disodium 3.5 H2O 298.2 mg equal to ceftriaxone 250 mg
TRUST 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use
• a bottle of powder contains:
active principle: ceftriaxone disodium 3.5 H2O 596.5 mg equal to ceftriaxone 500 mg
TRUST 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use
• a bottle of powder contains:
active principle: ceftriaxone disodium 3.5 H2O 1.193 g equal to ceftriaxone 1 g
TRUST 1 g / 10 ml powder and solvent for solution for injection for intravenous use
• a bottle of powder contains:
active principle: ceftriaxone disodium 3.5 H2O 1.193 g equal to ceftriaxone 1 g
TRUST 2 g powder for solution for infusion
• one bottle contains:
active principle: ceftriaxone disodium 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 FIDATO 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 adult dosage regimen does not require modification 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 FIDATO 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
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 practice the intramuscular injection, dissolve FIDATO im with the appropriate solvent (1% lidocaine solution) which is 2 ml for FIDATO 250 mg and 500 mg, and 3.5 ml for FIDATO 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 carry out the IV injection, dissolve FIDATO with the appropriate solvent (water for injections) which is 10 ml for FIDATO 1 g, and inject directly into a vein in 2-4 minutes.
Solution for infusion
To carry out intravenous perfusion, dissolve FIDATO at the rate of 2 g in 40 ml of calcium ion-free perfusion liquid (physiological solution, 5% or 10% glucose solution, 5% levulose solution, dextran glucose solution 6%).
The perfusion will last for at least 30 minutes.
FIDATO 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
FIDATO 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. 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 babies (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 shock cannot be excluded, even in the presence of an accurate patient history.
Each gram of FIDATO contains 3.6x mmol of sodium. To be taken into consideration in patients on a low sodium diet.
Diarrhea associated with Diarrhea has been reported with the use of nearly all antibacterial agents, including TRUSTED 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. difficult produces 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 FIDATO therapy. These findings have rarely been associated with symptoms. In symptomatic cases, non-surgical conservative management is recommended. In symptomatic cases, discontinuation of treatment with FIDATO should be at the discretion of the physician.
TRUST is eliminated for about 56% through the urine and the remaining 44% through 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 even in this circumstance the half-life is only slightly increased, in most cases it is not necessary to reduce the dosage of FIDATO, provided that the 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 combining more beta-lactamines.
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 initiating therapy with FIDATO, a thorough 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 organic functions, premature babies should not be treated with FIDATO doses higher than 50 mg / kg / day.
As for other antibiotics, prolonged use can favor the development of resistant bacteria and in case of superinfections 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. However, therapy with FIDATO can be started pending the results of these analyzes; and treatment should still be, if necessary, subsequently modified according to the results of the analyzes. Before using FIDATO 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 the lungs and kidneys in preterm and full-term newborns 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 have shown that neonates have an increased risk of calcium-ceftriaxone precipitation compared to other age groups.
In patients of any age, FIDATO should not be mixed or administered simultaneously with any calcium-containing intravenous solution, even through 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 FIDATO. 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 FIDATO-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 FIDATO in newborns, infants and children have been established for the dosages described in paragraph Dosage and administration. Clinical studies have shown that iceftriaxone, like some other cephalosporins, can remove bilirubin from serum albumin.
FIDATO should not be used in infants (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 simultaneous administration of high doses of FIDATO with high activity diuretics (eg furosemide) at high doses has not shown up to now disturbances in renal function. There is no evidence that FIDATO increases the renal toxicity of aminoglycosides. Ingestion of alcohol following FIDATO administration 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 FIDATO is not modified 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 FIDATO 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.
FIDATO must not be added to solutions that contain calcium, such as Hartmann 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 FIDATO vials or to further dilute a reconstituted vial for i.v. administration, as precipitate may form. Precipitation of calcium-ceftriaxone can also occur when FIDATO is mixed with calcium-containing solutions in the same IV administration line. FIDATO should not be administered concurrently 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, FIDATO and calcium-containing solutions can be administered in sequence, one after the other, provided that the lines are thoroughly rinsed with a compatible liquid between one "infusion" and the next. 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 FIDATO.
TRUST, 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 FIDATO therapy 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. Animal reproduction studies have shown no evidence of embryotoxicity, fetal toxicity 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 administering FIDATO 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
Because TRUST 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 20g 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.
The occurrence of anaphylactic shock is extremely rare and requires immediate countermeasures such as intravenous administration of adrenaline followed by a glucocorticoid.
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 FIDATO is pesudomembranous 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 can be symptomatic or asymptomatic, can cause renal failure and anuria and is reversible on discontinuation of FIDATO.
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
In patients treated with FIDATO, the Coombs test may rarely produce false positive results. Like other antibiotics, TRUSTED, it 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 FIDATO therapy must be performed enzymatically.
04.9 Overdose
In case of overdose, nausea, vomiting, 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 to TRUSTED of Gram-positive and Gram-negative pathogens can be evaluated 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, 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.
TRUST 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
• 1 bottle of powder + 1 solvent vial of 2 ml
TRUST 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use:
• 1 bottle of powder + 1 solvent vial of 2 ml
TRUST 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
TRUST 1 g / 10 ml powder and solvent for solution for injection for intravenous use:
• 1 bottle of powder + 1 solvent vial of 10 ml
TRUST 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
Fidia Farmaceutici S.p.A. - Via Ponte della Fabbrica, 3 / A - 35031 Abano Terme (PD)
08.0 MARKETING AUTHORIZATION NUMBER
FIDATO 250 mg / 2 ml powder and solvent for solution for injection for intramuscular use: 1 bottle of powder + 1 solvent ampoule - AIC n. 035867011
FIDATO 500 mg / 2 ml powder and solvent for solution for injection for intramuscular use: 1 bottle of powder + 1 solvent ampoule - AIC n. 035867023
TRUST 1 g / 3.5 ml powder and solvent for solution for injection for intramuscular use: 1 bottle of powder + 1 solvent ampoule - AIC n. 035867035
TRUST 1 g / 10 ml powder and solvent for solution for injection for intravenous use: 1 bottle of powder + 1 solvent ampoule - AIC n. 035867047
TRUST 2 g powder for solution for infusion: 1 bottle of powder - AIC n. 035867050
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
30/07/2004
10.0 DATE OF REVISION OF THE TEXT
AIFA determination of May 27, 2010
