Mesporin

Mesporin

ceftriaxone

Manufacturer:

Acino Switzerland

Distributor:

Ceutical Trading
/
Chong Ruan Trading
Full Prescribing Info
Contents
Ceftriaxone disodium.
Description
Mesporin contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone.
Sterile water for injection is the solvent used for the IV vial while 1% lidocaine HCl solution for the IM vial.
Action
Pharmacokinetics: Ceftriaxone displays nonlinear pharmacokinetics. All pharmacokinetic parameters, with the exception of the elimination half-life, are dose dependent if they refer to the overall concentration (free- and protein-bound ceftriaxone).
Absorption: After an IM injection of ceftriaxone 1 g, a maximum plasma concentration of 81 mg/L was achieved after 2-3 hrs. After a single IV infusion of 1 g, a concentration of 168.1±28.2 mg/L was achieved after 30 min. After a single IV infusion of 2 g, a concentration of 256.9±16.8 mg/L was achieved after 30 min.
The areas under the plasma concentration-time curves after IV and IM administration are identical. This means that the bioavailability of ceftriaxone administered IM is 100%.
Distribution: The distribution volume lies between 7 and 12 L.
With IV administration, ceftriaxone rapidly penetrates interstitial body fluids, where bactericidal concentrations remain active against sensitive pathogens for 24 hrs.
After a dose of 1-2 g, ceftriaxone shows good penetration into tissue and body fluids; concentrations above the minimal inhibitory concentration for most pathogens were measured for >24 hrs in over 60 tissues and body fluids, including lungs, heart, biliary tract, liver, middle ear, nasal mucous membrane and bones as well as cerebrospinal, pleural, synovial and prostate fluid.
Ceftriaxone is reversibly bound to plasma albumin, and the binding decreases with the increase in the concentration eg, 95% binding at plasma concentrations of <100 mg/L to 85% binding at a plasma concentration of 300 mg/L. Owing to the lower albumin content, the proportion of free ceftriaxone in the interstitial fluid is correspondingly higher than in plasma.
Ceftriaxone penetrates the inflamed meninges of infants and children. An average maximal concentration of 18 mg/L in the CSF is reached approximately 4 hrs after IV application of ceftriaxone 50-100 mg/kg. The average extent of diffusion into the CSF in bacterial meningitis is about 17% of the plasma concentration; in aseptic meningitis, 4%. Twenty-four hours after injection of ceftriaxone in doses of 50-100 mg/kg body weight, concentrations of >1.4 mg ceftriaxone/L have been found in the CSF. In adult patients with meningitis, administration of 50 mg/kg leads within 2-24 hrs to CSF concentrations which are several times higher than the required minimal inhibitory concentration against the most common causative organisms in meningitis.
Ceftriaxone penetrates the placental barrier. Ceftriaxone is excreted into breast milk in low concentrations (3-4% of the mother's plasma concentration after 4-6 hrs).
Metabolism: Ceftriaxone is not metabolized in the organism itself. Bowel flora converts the active agent into inactive metabolites after biliary excretion into the lumen of the bowel.
Elimination: Plasma clearance is 10-22 mL/min. Renal clearance is 5-12 mL/min. In adults, 50-60% of ceftriaxone is excreted in the urine as unchanged drug while 40-50% is excreted unchanged in the bile. The serum elimination half-life in healthy subjects is about 8 hrs.
Special Clinical Situations: In neonates, renal elimination accounts for about 70% of the dose. In infants <8 days and subjects >75 years, the average elimination half-life is about 2-3 times as long. The pharmacokinetics of ceftriaxone are only minimally altered in patients with renal impairment or hepatic dysfunction, and the elimination half-life is only slightly increased. If kidney function alone is impaired, biliary elimination of ceftriaxone is increased; hepatic dysfunction alone leads to increased renal excretion.
Long-acting, broad-spectrum bactericidal antibiotic.
Microbiology: The bactericidal activity of ceftriaxone results from inhibition of cell wall synthesis. Ceftriaxone exerts in vitro activity against a wide range of gram-negative and gram-positive microorganisms. It is highly stable to most β-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria. Ceftriaxone is usually active against the following microorganisms in vitro and in clinical infections: See Table 1.

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Susceptibility Testing: Susceptibility to ceftriaxone can be determined by the disk diffusion test or by the agar or broth dilution test using standardised techniques for susceptibility testing eg, those recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The NCLLS issued the following interpretative breakpoints for ceftriaxone: See Table 2.

Click on icon to see table/diagram/image

Microorganisms should be tested with the ceftriaxone disk since it has been shown by in vitro tests to be active against certain strains resistant to cephalosporin class disks.
Where NCLLS recommendations are not in daily use, alternative, well standardised, susceptibility interpretative guidelines eg, those issued by DIN, ICS and others may be substituted.
Resistances: Some isolates of this species are resistant to ceftriaxone because of the dereprimation of the chromosomal β-lactamase; some isolates of Klebsiella pneumoniae are resistant to ceftriaxone because of the plasmid-dependent β-lactamase production; some isolates of Bacteroides sp are resistant to ceftriaxone.
Many strains of the β-lactamase-producing Bacteroides sp (specifically B. fragilis) are resistant.
Clostridium difficile is resistant.
Methicillin-resistant Staphylococcus sp are resistant to cephalosporins including ceftriaxone. Enterococcus faecalis and Enterococcus faecium as well as Listeria monocytogenes are resistant as a rule.
Many strains of gram-negative aerobes demonstrating multiple resistance to other antibiotics eg, amino- and ureido-penicillins, older cephalosporins and aminoglycosides are sensitive to ceftriaxone. Treponema pallidum is sensitive in vitro and in animal experiments. Clinical trials have shown that primary and secondary syphilis responds well to treatment with ceftriaxone.
With few exceptions, clinical isolates of Pseudomonas aeruginosa are resistant to ceftriaxone.
Indications/Uses
Treatment of infections caused by strains susceptible to ceftriaxone, in the conditions listed as follows: Respiratory tract infections, particularly pneumonia and ear, nose and throat infections; abdominal infections (peritonitis, infections of the biliary tract and the gastrointestinal tract); renal and urinary tract infections; infections of the genital tract and organs, including gonorrhoea; sepsis; infections of the bones, joints, soft tissues, skin and wounds; infections in immunocompromised patients; meningitis; disseminated Lyme borreliosis (stage II and III); perioperative infection prophylaxis in operations of the GI tract, biliary tract, in urogenital and gynecological procedures, however, only in case of potential or established contamination.
Dosage/Direction for Use
Recommended Dosage: Adults and Children >12 years: The usual dosage is 1-2 g of ceftriaxone once daily (every 24 hrs). In severe infections, or infections caused by moderately susceptible pathogens, the daily single dose may be raised to 4 g.
The following dosage schedules are recommended for once-daily administration:
Infants and Children (3 weeks to 12 years): A daily dose of 20-80 mg/kg. For children with a body weight of ≥50 kg, the usual adult dosages should be used. IV doses of ≥50 mg/kg body weight should be given by infusion over at least 30 min.
Neonates (up to 2 weeks): A daily dose of 20-50 mg/kg body weight; not to exceed 50 mg/kg. It is not necessary to differentiate between premature babies and infants born at term.
Elderly: The recommended dosages for adults do not require modification.
Duration of Treatment: Duration of treatment varies according to the indication and the course of the illness.
Combination Therapy: Synergy between aminoglycosides and ceftriaxone has been demonstrated experimentally with many gram-negative bacteria. Although enhanced activity of such combinations is not always predictable, it should be considered in severe, life-threatening infections caused by pathogens eg, Pseudomonas aeruginosa. Because of physical incompatibility, the 2 drugs must be administered separately at the recommended dosage.
Special Dosage Instructions: Meningitis: In bacterial meningitis in infants and children, the treatment begins with doses of 100 mg/kg (not to exceed 4 g) once daily. As soon as the causative organism has been identified and its sensitivity determined, the dosage can be reduced accordingly. The best results have been found with the following duration of treatment: Neisseria meningitidis: 4 days; Haemophilus influenzae: 6 days; Streptococcus pneumoniae: 7 days.
Lyme Borreliosis: The dosage for the treatment of Lyme borreliosis in children and adults is 50 mg/kg to a maximum of 2 g once daily during 14 days.
Gonorrhoea: For the treatment of gonorrhoea (penicillinase- and nonpenicillinase-producing strains), the single IM administration of 250 mg of ceftriaxone is recommended.
Perioperative Prophylaxis: To prevent postoperative infections in contaminated or potentially contaminated surgical procedures, it is recommended, depending on risk of infection, to administer a single dose of 1-2 g of ceftriaxone 30-90 min prior to surgery. In colorectal surgery, the simultaneous (but separate) administration of ceftriaxone and a 5-nitroimidazole eg, ornidazole is recommended.
Impaired Renal and Liver Function: In patients with impaired renal function, there is no need to reduce the dosage of ceftriaxone, provided liver function is intact. Only in cases of preterminal renal failure (creatinine clearance <10 mL/min), the daily dose of ceftriaxone must not exceed 2 g. In patients with impaired liver function, there is no need to reduce the dose of ceftriaxone, provided renal function is intact. In cases of concomitant severe renal and liver dysfunction, the plasma concentration of ceftriaxone should be determined at regular intervals. Dosage adjustment may be required as these patients can show a reduced elimination of ceftriaxone. In patients undergoing dialysis, no supplementary dosing is required after dialysis. More important, the serum concentration should be monitored to determine if dosage adjustments are necessary, as these patients may have a reduced elimination rate. A daily dose of 2 g should not be exceeded in patients undergoing dialysis.
Administration: IM Injection: For IM injection, Mesporin should be dissolved in the appropriate volume of solvent as follows: 250 or 500 mg of ceftriaxone in 2 mL of 1% lidocaine solution; 1 g of ceftriaxone in 3.5 mL of 1% lidocaine solution, administered by deep IM injection. It is recommended that no more than 1 g of ceftriaxone should be injected on either side. The lidocaine solution must never be administered IV.
IV Injection: For IV injection, 1 g of ceftriaxone is dissolved in 10 mL of sterile water for injection and administered by slow IV injection lasting 2-4 min.
IV Infusion: The infusion should last for at least 30 min. 2 g Mesporin are dissolved in 40 mL of one of the following calcium-free infusion solutions for IV infusion: Sodium chloride 0.9%, sodium chloride 0.45% + glucose 2.5%, glucose 5%, glucose 10%, dextran 6% in glucose 5%, hydroxyethyl starch 6-10%, water for injection purposes. Because of possible incompatibility, solutions containing Mesporin must not be mixed with or joined to solutions containing other antibiotics, and must not be added to infusion solutions other than those listed previously. However, 2 g ceftriaxone and 1 g ornidazole are physically and chemically compatible in 250-mL physiological sodium chloride or glucose solution.
The physical and chemical stability of reconstituted solutions is retained for 6 hrs at room temperature (or 24 hrs at 5°C). However, as a general rule, the solutions should be used immediately after preparation. Depending on the concentration, solvent used and length of storage, the color of the solutions ranges from light yellow to amber. This property of ceftriaxone has no significance to the efficacy or tolerance of the drug.
Overdosage
Excessively high plasma concentrations of ceftriaxone cannot be reduced through haemo- or peritoneal dialysis. Symptomatic measures are recommended for treating patients after overdosage.
Contraindications
Patients with known allergy to the cephalosporin class of antibiotics. Mesporin should be given cautiously to penicillin-sensitive patients; the possibility of allergic cross-reactions should be borne in mind.
Special Precautions
Even after a detailed medical history has been established, an anaphylactic reaction cannot be excluded.
If allergic reactions occur, Mesporin must be discontinued immediately and suitable therapy initiated.
Ceftriaxone can prolong prothrombin time. In case of a suspected vitamin K deficit, a check of the quick value is therefore recommended.
In the case of severe or lasting diarrhoea, pseudomembranous colitis caused by antibiotics and potentially life-threatening, must be taken into consideration.
Therefore, in this case, Mesporin must be discontinued immediately and suitable therapy initiated.
In the case of long-term use of Mesporin, nonsensitive pathogens may supervene. Therefore, close monitoring of the patient is essential. If a superinfection occurs during treatment, appropriate measure must be taken.
During ultrasound investigations of the gallbladder, shadows can mistakenly be interpreted as gallstones. Such shadows are generally precipitation of the calcium salt of ceftriaxone. This precipitation has usually occurred when doses higher than those recommended were administered. When treatment with Mesporin ends or is interrupted, these shadows disappear.
These findings were rarely accompanied by symptoms. In cases where symptoms occur, conservative, nonsurgical treatment is recommended. The doctor should decide whether to discontinue Mesporin in patients with symptoms.
In rare cases, there have been reports of pancreatitis possibly caused by cholestasis in patients treated with Mesporin. Most patients showed risk factors for cholestasis and bile slime in consultation eg, extensive previous treatment, serious illness or completely parenteral diet. It cannot be excluded that the precipitation stemming from Mesporin in the gallbladder can be a trigger or a co-factor. Ceftriaxone can displace bilirubin from its binding to serum albumin. Care is therefore necessary when treating newborn babies with hyperbilirubinaemia.
Newborn, and in particular, prematurely born patients with the risk of bilirubin encephalopathy should not be treated with Mesporin.
The blood picture should be checked regularly during long-term treatment. Care must be taken with patients with impaired renal function in the case of concomitant treatment with aminoglycosides and diuretics.
Use in pregnancy & lactation: Pregnancy Category B: Ceftriaxone penetrates the placental barrier (see Pharmacokinetics: Distribution under Actions). Although neither mutagenic nor teratogenic characteristics have been established in the corresponding preclinical examinations, Mesporin should only be used in the case of imperative need during pregnancy, particularly in the first 3 months.
Because ceftriaxone is excreted into breast milk, even if only in low concentrations, care must be taken in treating lactating women with Mesporin.
Use In Pregnancy & Lactation
Pregnancy Category B: Ceftriaxone penetrates the placental barrier (see Pharmacokinetics: Distribution under Actions). Although neither mutagenic nor teratogenic characteristics have been established in the corresponding preclinical examinations, Mesporin should only be used in the case of imperative need during pregnancy, particularly in the first 3 months.
Because ceftriaxone is excreted into breast milk, even if only in low concentrations, care must be taken in treating lactating women with Mesporin.
Adverse Reactions
During treatment with ceftriaxone, the following adverse reactions were observed, which disappeared either spontaneously or after withdrawal of treatment.
Systemic Tolerance: Gastrointestinal Complaints (about 2% of cases): Loose stools or diarrhoea, nausea, vomiting, stomatitis and glossitis.
Haematological Changes (about 2%): Eosinophilia, leukopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia, prolongation of the prothrombin time, isolated cases of agranulocytosis (<500/mm3) have been observed, most of them after total doses of ≥20 g.
Skin Reactions (about 1-2%): Exanthema, allergic dermatitis, pruritus, urticaria and oedema. There have been reports of isolated cases of severe skin reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis).
Others: Headache and dizziness, increased liver enzymes, oliguria, increase in serum creatinine, mycosis of the genital tract, fever, shivering, and anaphylactic or anaphylactoid reactions, as well as precipitation of the calcium salt of ceftriaxone in the gallbladder.
Pseudomembranous enterocolitis and prolongation of the prothrombin time have been reported as very rare adverse effects.
Precipitation in the kidneys has been very rarely observed, and usually in children >3 years who were treated with either high daily doses (eg, ≥80 mg/kg/day) or overall doses in excess of 10 g and showing other risk factors (eg, reduced fluid intake, confinement to bed, etc). This adverse effect can occur with or without symptoms, can lead to renal insufficiency and is reversible after discontinuation of Mesporin.
Local: Phlebitis <1% after IV administration. This can be avoided by slow IV injection (2-4 min). IM injection without lidocaine solution is painful.
Drug Interactions
After simultaneous administration of high doses of ceftriaxone and potent diuretics eg, furosemide, no disturbance of renal function has been observed. A "disulfiram-like" effect after ceftriaxone administration and concomitant intake of alcoholic beverages has not been demonstrated. Ceftriaxone does not contain an N-methylthiotetrazole moiety that may cause ethanol intolerance and bleeding problems, as is the case with some other cephalosporins. Probenecid has no influence on the elimination of ceftriaxone.
There is no proof that ceftriaxone increases the renal toxicity of aminoglycosides. Bacteriostatic agents can interfere unfavourably with the bactericidal effect of cephalosporins.
Antagonistic effects have been observed in an in vitro study of ceftriaxone in combination with chloramphenicol.
Incompatibilities: Mesporin must not be mixed with solutions containing calcium eg, Hartmann's or Ringer's solution.
Ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole and aminoglycosides.
Influence on Diagnostic Methods: In rare cases under treatment with Mesporin, the Coombs' test can give a false positive result. Tests for galactosemia can give a false positive result under Mesporin as is the case with other antibiotics.
Non-enzymatic methods for determining urinary sugar can also give a false positive result. For this reason, urinary sugar should be determined enzymatically during therapy with Mesporin.
MIMS Class
ATC Classification
J01DD04 - ceftriaxone ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.
IV: A, IM: P1, A
Presentation/Packing
IM vial 250 mg/2 mL x 1's. 500 mg/2 mg x 1's. 1 g/3.5 mL x 1's. IV vial 1 g/10 mL x 1's.
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