ROSS 1000
-
Chemical Name:
Ceftriaxone (Sodium) -
Therapeutic Category:
Antimicrobial -
Pharmacologic Category:
Antibiotic, Cephalosporin (Third Generation) -
Pharmaceutical Form:
Vial -
Composition:
Ceftriaxone (Sodium) 1000mg
ROSS
For Injection (Vial)
Ceftriaxone (Sodium)
1-PROPERTIES :
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. Ceftriaxone is highly stable to most B-lactamases, both penicillinases and cephalosporinases, of gram-positive and gram-negative bacteria. Ceftriaxone is usually active against the following microorganisms in vitro and in clinical infections:
Gram-positive aerobes: Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus group A (Str. Pyogenes), Streptococcus group B (Str. Agalactiae), Streptococcus viridans, Streptococcus bovis.
Note: Methicillin-resistant Staphylococcus spp. are resistant to cephalosporins, including ceftriaxone. Most strains of Enterococci (e.g., Streptococcus faecalis) are resistant.
Gram-negative aerobes: Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp., Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp, Moraxella spp., Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Salmonella spp., (including S. typhi), Serratia spp., (including S. marcescens), Shigella spp., Vibrio spp. (including V. Cholerae), Yersinia spp. (including Y. Enterocolitica).
Note: Many strains of the above microorganisms that are multiply resistant to other antibiotics, e.g., penicillins, older cephalosporins and aminoglycosides, are susceptible to ceftriaxone.
Treponema pallidum is sensitive in vitro and in animal experiments. Clinical investigations indicate that primary and secondary syphilis respond well to ceftriaxone therapy.
Anaerobic organisms: Bacteroides spp. (including some strains of B. fragilis), Clostridium spp. (except CI. Difficile), Fusobacterium spp. (except F. mortiferum and F. varium), Peptococcus spp., Peptostreptococcus spp.
Note: Many strains of B-lactamase-producing Bacteroides spp. (notably B. fragilis) are resistant.
2-PHARMACOKINETICS:
Ceftriaxone is characterized by an unusually long elimination half-life of approximately eight hours in healthy adults. The area under the plasma concentration time curves after i.v. and i.m. administration is identical. This means that the bioavailability of ceftriaxone administered by i.m. is 100%. On intravenous administration, ceftriaxone diffuses rapidly into the interstitial fluid, where bactericidal concentrations against susceptible organisms are maintained for 24 hours.
Concentration after 1g ROSS:
Elimination: The elimination half-life in healthy adults is about eight hours, in infants and new born and in adults over 75 years of age, the average elimination half-life is about twice as long.
In adults, 50-60% of ceftriaxone is excreted unchanged by the kidneys, while 40-50% is excreted unchanged in the bile. The intestinal flora transforms ceftriaxone into inactive metabolites. In neonates, renal elimination accounts for about 70% of the dose. In patients with renal impairment or hepatic dysfunction, the pharmacokinetics of ceftriaxone are only minimally altered and the elimination half-life is only slightly increased. If kidney function alone is impaired, biliary elimination of ceftriaxone is increased. if liver function alone is impaired, renal elimination is increased.
Protein binding: Ceftriaxone is reversibly bound to albumin, and the binding decreases with the increase in the concentration, e.g. from 95% binding at plasma concentrations of <100 mg/l to 85% binding at 300 mg/l. Owing to the lower albumin content, the proportion of free ceftriaxone in interstitial fluid is correspondingly higher than in plasma.
Penetration into the cerebrospinal fluid: Ceftriaxone penetrates the inflamed meninges of infants and children. The average extent of diffusion in the cerebrospinal fluid in bacterial meningitis is 17% of the plasma concentration, i.e. approximately four times that in aseptic meningitis. Ceftriaxone concentrations of > 1.4mg/l have been found in the CSF 24 hours after i.v. injection of ROSS in doses of 50-100 mg/kg. In adult meningitis patients, administration of 50 mg/kg leads within 2-24 hours to CSF concentrations several times higher than the minimum inhibitory concentrations required for the most common causative organisms of meningitis.
3-INDICATIONS:
ROSS is prescribed in the following infections caused by pathogens sensitive to ceftriaxone:
- Septicemia.
- Meningitis
- Abdominal infections (peritonitis, infections of the biliary and gastrointestinal tracts).
- Infections of the bones, joints, soft tissue, skin and of wounds.
- Infections in patients with impaired defence mechanisms.
- Renal and urinary tract infections.
- Upper and lower respiratory tract infections, particularly pneumonia, and ear, nose and throat infections.
- Genital infections, including gonorrhea.
Perioperative prophylaxis of infections.
4- CONTRAINDICATIONS:
ROSS is contraindicated in patients with known hypersensitivity to the cephalosporin class of antibiotics. In patients hypersensitive to penicillin, the possibility of allergic crossreactions should be born in mind.
ROSS should not be used in pregnancy (particularly in the first trimester) unless absolutely indicated.
5-PRECAUTIONS:
As with other cephalosporins, anaphylactic shock cannot be ruled out even if a thorough patient history is taken. Anaphylactic shock requires immediate countermeasures such as intravenous epinephrine followed by a glucocorticoid etc…
In rare cases, shadows suggesting sludge have been detected by sonograms of the gallbladder. This condition was reversible on discontinuation or completion of ROSS therapy. Even if such findings are associated with pain, conservative, nonsurgical management is recommended.
In-vitro studies have shown that ceftriaxone, like some other cephalosprins, can displace bilirubin from serum albumin. Caution should be exercised when considering ROSS for hyperbilirubinemic neonates, especially prematures.
During prolonged treatment the blood picture should be checked at regular intervals.
Pregnancy: ROSS should not be used in pregnancy particularly in the first trimester, unless absolutely indicated.
6-UNDESIRABLE EFFECTS:
ROSS is generally well tolerated. During the use of ROSS, the following side effects, which were reversible either spontaneously or after withdrawal of the drug, have been observed.
Systemic side effects:
Gastrointestinal complaints (about 2% of cases): Loose stools or diarrhea, nausea, vomiting, stomatitis and glossitis.
Hematological changes (about 2%): Eosinophilia, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia.
Skin reactions (about 1%): Exanthema, allergic dermatitis, pruritus, urticaria, edema, erythema multiforme.
Other, rare side effects: Headache and dizziness, increase in liver enzymes, gallbladder sludge, oliguria, increase in serum creatinine, mycosis of the genital tract, shivering and anaphylactic or anaphylactoid reactions.
Pseudomembranous enterocolitis and coagulation disorders have been reported as very rare side effects.
Local side effects: In rare cases, phlebitic reactions occurred after i.v. administration. This may be prevented by slow (two to four minutes) injection of the substance.
Intramuscular injection without lidocaine solution is painful and contraindicated.
7-DRUG INTERACTIONS:
No impairment of renal function has so far been observed after concurrent administration of large doses of ROSS and potent diuretics (e.g. furosemide). There is no evidence that ROSS increases renal toxicity of aminoglycosides. No effect similar to that of disulfiram has been demonstrated after ingestion of alcohol subsequent to the administration of ROSS.
The elimination of ROSS is not altered by probenecid.
8-DOSAGE & ADMINISTRATION:
STANDARD DOSAGE:
Adults and children over 12 years: The usual dosage is 1-2g of ROSS administered once daily (every 24 hours). In severe cases or in infections caused by moderately sensitive organisms, the dosage may be raised to 4 g, administered once daily.
Neonates (up to 2 weeks): A daily dose of 20-50 mg/kg bodyweight, not to exceed 50 mg/kg, on account of the immaturity of the infant’s enzyme systems.
Infants and children (3 weeks to 12 years): A daily dose of 20-80 mg/kg body weight.
For children with bodyweights of 50 kg or more: The usual adult dosage should be used.
Intravenous doses of 50 mg or more per kg should be given by infusion over at least 30 minutes.
Duration of therapy: The duration of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of ROSS should be continued for a minimum of 48-72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.
Combination therapy: Synergy between ROSS and aminoglycosides has been demonstrated with many gram-negative bacilli under experimental conditions. Although enhanced activity of such combinations is not always predictable, it should be considered in severe, life-threatening infections due to microorganisms such as Pseudomonas aeruginosa. Because of physical incompatibility the two drugs must be administered separately at the recommended dosages.
SPECIAL DOSAGE INSTRUCTIONS:
Meningitis: In bacterial meningitis in infants and children, treatment begins with doses of 100mg/kg (not to exceed 4g) 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 therapy:
Neisseria meningitis: 4 days, Streptococcus pneumonia: 7 days, Haemophilus influenza: 6 days, Susceptible Enterobacteriaceae: 10-14 days.
Gonorrhea: For the treatment of gonorrhea, a single i.m. dose of 250 mg ROSS is recommended.
Perioperative prophylaxis: To prevent postoperative infections in contaminated or potentially contaminated surgery, the recommended approach (depending on the risk of infection) is a single dose of 1-2 g ROSS administered 30-90 minutes prior to surgery.
Impaired renal and hepatic function: In patients with impaired renal function, there is no need to reduce the dosage of ROSS provided hepatic function is intact. Only in cases of preterminal renal failure (creatinine clearance < 10ml/min) should the ROSS dosage not exceed 2 g daily. In patients with liver damage, there is no need for the dosage to be reduced provided renal function is intact.
In cases of concomitant severe renal and hepatic dysfunction, the plasma concentrations of ceftriaxone should be determined at regular intervals.
In patients undergoing dialysis no additional supplementary dosing is required following the dialysis. Serum concentrations should be monitored, however, to determine whether dosage adjustments are necessary, since the elimination rate in these patients may be reduced.
Note: ROSS could be used by I.M. route only if dissolved in lidocaine 1% solution.
ADMINISTRATION:
Reconstituted solutions retain their physical and chemical stability for six hours at room temperature (or 24 hours at 5˚C) . As a general rule, however, the solutions should be used immediately after preparation. They range in colour from pale yellow to amber, depending on the concentration and the length of storage. This characteristic of the active ingredient is of no significance for the efficacy or tolerance of the drug.
Intramuscular injection: For i.m. injection, ROSS 250 mg is dissolved in 1 ml and 0.5 g is dissolved in 2 ml, ROSS 1 g in 3.5 ml, and ROSS 2 gr in 7ml of 1% lidocaine solution and administered by deep intragluteal injection. It is recommended that not more than 1 g be injected on either side.
The lidocaine solution must never be administered intravenously.
Intravenous injection: For i.v. injection, ROSS 250 mg is dissolved in 3 ml, ROSS 0.5 g is dissolved in 4 ml, ROSS 1 g in 6 ml, and ROSS 2 gr in 8 ml of sterile water for injections, and then administered by i.v. injection lasting 2 to 4 minutes.
Intravenous infusion: The infusion should last at least 30 minutes. For i.v. infusion, 2g ROSS are dissolved in 40 ml of one of the following calcium free-infusion solutions: sodium chloride 0.9%, sodium chloride 0.45% + dextrose 2.5%, dextrose 5%, dextrose10%, levulose 5%, dextran 6% in dextrose, sterile water for injections. ROSS solutions, should not be mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed above, owing to possible incompatibility.
9-PACKAGING & COMPOSITION:
- ROSS 250 – For Injection: A pack of 1 or 10 vials. Each vial contains sterile Ceftriaxone Sodium equivalent to Ceftriaxone 250 mg.
- ROSS 500 – For Injection: A pack of 1 or 10 vials. Each vial contains sterile Ceftriaxone Sodium equivalent to Ceftriaxone 500 mg.
- ROSS 1000 – For Injection: A pack of 1 or 10 vials. Each vial contains sterile Ceftriaxone Sodium equivalent to Ceftriaxone 1000 mg.
- ROSS 2000 – For Injection: A pack of 1 or 10 vials. Each vial contains sterile Ceftriaxone Sodium equivalent to Ceftriaxone 2000 mg.
10-STORAGE CONDITIONS:
Store ROSS - For Injection at temperature below 25°C. Protect from light.
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