Modern Pharma Company

17 May

Rozin 500

Antibiotics & Antibacterial

- Ceftriaxone is a sterile, semisynthetic, long acting, broad spectrum antibiotic
belong to third generation cephalosporins.
- Ceftriaxone inhibits bacterial cell wall synthesis following attachment to
penicillin binding proteins. This results in the interruption of cell wall
(peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
- Ceftriaxone exerts in vitro activity against a wide range of Gram-negative and
Gram-positive micro-organisms.
- Ceftriaxone is usually active in-vitro and in clinical infections against the
following:
Gram-positive aerobes: Staphylococcus aureus, Staphylococcus epidermi-
dis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus
agalactiae, Streptococcus viridans, Streptococcus bovis.
Gram-negative aerobes: Aeromonas spp., Alcaligenes spp., Branhamella
catarrhalis, citrobacter spp., Enterobacter spp. (some strains are resistant), 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., Pseud-
omonas aeruginosa (some strains are resistant), Salmonella spp., serratia
spp., Shigella spp., Vibrio spp., Yersinia spp.
Anaerobic organisms: Bacteroides spp.,Clostridium spp. (except Cl. diffi-
cile ), Fusobacterium spp. (except F. mortiferum and F. varium ),Peptococ-
cus spp., Peptostreptococcus spp.
Note: Many strains of ß-lactamase-producing Bacteroides spp. (notably B.
fragilis) are resistant.
- Ceftriaxone is highly stable to most ß-lactamases, both penicillinases and
cephalosporinases, of Gram-positive and Gram-negative bacteria.
- The area under the plasma concentration time curves after l.V. and l.M.
administration of Ceftriaxone is identical. This means that the bioavailability
of ceftriaxone administered l.M, is 100%. On intravenous administration,
ceftriaxone diffuses rapidly into the interstitial fluid, where bactericidal
concentrations against susceptible organisms are maintained for 24 hours.
-Ceftriaxone is reversibly bound to albumin, and the binding decreases with
the increase in the concentration. The average extent of diffusion in the
cerebrospinal fluid in bacterial meningitis is 17% of the plasma concentration.
- In patients with renal impairment or hepatic dysfunction, the pharmacokinet-
ics of ceftriaxone are 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.
- Ceftriaxone is characterized by an unusually long elimination half-life of
approximately eight hours in healthy adults. In infants aged less than eight
days and in persons 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. In neonates, renal elimination
accounts for about 70% of the dose.

Indecation

- Infections caused by pathogens sensitive to ROZIN® e.g.: Sepsis; meningitis;
abdominal infections (peritonitis, infections of the biliary and gastro-
intestinaltracts); infections of the bones, joints, soft tissue, skin and of
wounds; infections in patients with impaired defence mechanisms; renal and
urinary tract infections; respiratory tract infections, particularly pneumonia, and
ear, nose and throat infections; genital infections, including gonorrhea.
- Perioperative prophylaxis of infections.

Dosage & Administration

After reconstitution, ROZIN® is administered by intermittent intravenous
injection and by deep intramuscular injection.
• Adults and children over 12 years: The usual dosage is 1-2 g of ROZIN®
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.
• Infants and Children (3 weeks to 12 years): A daily dose of 20-80 mg/kg.
Intravenous doses of 50 mg/kg or more should be given by infusion over at
least 30 minutes.
• Elderly patients: The dosage recommended for adults require no modifica-
tion in the case of geriatric patients.
• Special dosage instructions:
- Meningitis: In bacterial meningitis in infants and children, treatment
begins with doses of 100 mg/kg (not to exceed 4 g) once daily. The best results
have been found with the following duration of therapy:
- Gonorrhea: A single IM dose equivalent to 500 mg ROZIN® .
- Perioperative prophylaxis: A single dose of 1-2 g ROZIN® administered
30-90 minutes prior to surgery.
- Impaired renal function: Only in cases of preterminal renal failure
(creatinine clearance <10 ml/min) should the ROZIN® dosage not exceed
2 g daily.
- Impaired hepatic function: No need for the dosage to be reduced.
- Reconstitution: Reconstituted solutions retain their physical and chemical
stability for 6 hours at room temperature or for 24 hours at 5ºC. As a
general rule; however, the solutions should be used immediately after
preparation. They range in color from pale yellow to amber (depending on
the concentration and the length of storage), this is of no significance for the
efficacy or tolerance of the drug.
Intramuscular injection: ROZIN® 500 mg is dissolved in 1.8 ml of 1%
lidocaine solution, and ROZIN® 1 g in 3.6 ml of 1% lidocaine solution,
and administered by deep intra-muscular injection. Intramuscular injection
without lidocaine solution is painful.
Intravenous injection: ROZIN® 500 is dissolved in 4.8 ml of sterile water
for injection and ROZIN® 1000 in 9.6ml of sterile water for injection and

then administered by I.V. injection lasting 3 to 5 minutes.

Composition

- Each vial of ROZIN® 500 mg contains:
Ceftriaxone 500 mg (as Ceftriaxone Sodium)
- Each vial of ROZIN® 1 g contains:
Ceftriaxone 1 g (as Ceftriaxone Sodium)

Contraindecation

- ROZIN® is contraindicated in patients with known hypersensitivity to the
cephalosporin class of antibiotics. In patients hypersensitive to penicillin, the
possibility of allergic cross reactions should be borne in mind.

Drug Interaction

No impairment of renal function has so far been observed after simultanous
administration of larger doses of Ceftriaxone and potent diuretics like
furosemide.There is no evidence that Ceftriaxone increases renal toxicity of
aminoglycosides. No effect similar to that of disulfiram has been
demonstrated after administration of alcohol with Ceftriaxone. The
elimination of Ceftriaxone is not altered by probenecid.

Pregnancy & Lactation

Ceftriaxone should not be used in pregnancy (particularly in the first trimester)
unless absolutely indicated. Low concentrations of ceftriaxone are excreted in
human milk, caution should be exercised when ROZIN® is administered to a
nursing woman.

Side Effects

- ROZIN® is generally well tolerated. The following side effects may arise:
diarrhea, nausea, vomiting, stomatitis, glossitis, eosinophilia, leukopenia,
granulocytopenia, hemolytic anemia, thrombocytopenia, pruritus, urticaria,
erythema multiforme, headache and dizziness, increase in liver enzymes. In rare
cases, phlebitic reactions occurred after I.V. administration. These may be
prevented by slow (2 - 4 minutes) injection of the substance.

Precaution

- Prolonged use of antibiotics may result in over-growth of non-susceptible
organisms.
- Because Ceftriaxone can displace bilirubin from serum albumin, it should
not be administered to hyperbilirubinemic neonates, particularly those who
are premature. Alterations in prothrombin times have been reported only rarely in patients receiving Ceftriaxone. Patients with impaired vitamin K
synthesis or low vitamin K stores (e.g. chronic hepatic disease, malnutrition)
may require monitoring of prothrombin time during Ceftriaxone treatment.
10 mg of vitamin K weekly may be necessary if the prothrombin time is
prolonged before or during therapy.

Storage

- Store below 25ºC, and protect from light.