Epicephin vial composition :
Active ingredient: ceftriaxone (as the disodium salt).
Epicephin vial indications and potential uses :
Infections caused by pathogens which are susceptible to ceftriaxone, e.g.:
– respiratory tract infections, particularly pneumonia, and ear, nose and throat infections;
– abdominal infections ( infections of the biliary and gastrointestinal tracts);
– renal and urinary tract infections; infections or the genital organs, gonorrhea;
– infections of the bones, soft tissue and skin, and wound infections
– meningitis
– disseminated Lyme borreliosis (stages II and lll).
Perioperative prophylaxis of infections in operations on the gastrointestinal tract, biliary tract and urogenital tract and in gynecological procedures, but only in cases of potential or known contamination. Official recommendations on appropriate use of antibiotics should be observed, in partlcutar recommendations on how to prevent increased antibiotic resistance.
Epicephin vial dosage and administration :
Epicephin vial Dosage:
Adults and children over 12 years: The usual dosage is 1 – 2 g of
Epicephin: once daily {every 24 hours). In severe cases or in infections caused by only moderately sensitive organisms, the dosage may be increased to 4 g once daily.
Neonates, Infants and children up to 12 years: The following dosage guidelines are recommended for once-dally administration:
Neonates (up to 14 days): A daily dose of 20 – 50 mg/kg body weight 50 mg/kg should not be exceeded. It is not necessary differentiate between ptemature infants and those born at term.
Eplcephin: is contraindicated In neonates is 28 days) if they require infusions such as in parenteral nutrition, because of the risk of calcium ceftriaxone precipitation (see contraindications).
Infants and children ( days to 12 years): A daily dose of 20 – 80
For children with abody weight of 50 kg or more, the usual adult dosage should be used .
Intravenous doses of 50 mg or more per kg bodyweight should be given by stow infusion over at least 30 minutes.
Elderly patients: The dosages recommended for adults require no modification in the case of geriatric patients.
Duration of therapy: The duration of therapy varies with the indication and the course of the disease.
Combination therapy: Synergy between Epicephin and aminogiycosides has been demonstrated with many gram-negative bacteria under experimental conditions. Although enhanced activity of such combinations is not always predictable, combination 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 the case of bacterial meningitis in infants and children, treatment begins with doses of 100 mg/kg (not to exceed 4
once daily. Once the pathogen has been identified and its sensitivity determined, the dosage can be reduced accordingly. Best results have been achieved with the following durations of therapy:
Neisseria meningitides 4 days
Haemophilus influenzae 6 days
Streptococcus pneumoniae 7 days
Lyme borreliosis: The dosage in Lyme borreliosis is 50 mg/kg up to
a maximum of 2 g in children and adults, administered once daily for 14 days.
Conorrhea: For the treatment of gonorrhea (penicillinase – producing and non – penicillinase – producing strains), a single I.M.
dose of 0.25 g Epicephin is recommended.
Perioperative prophylaxis: To prevent postoperative infection in contaminated or potentially contaminated operations, a single dose of 1-2 g Epicepbin – depending on the risk of infection – is recommended for administration 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 Epicephin,
provided hepatic function is not impaired. However, in cases of preterminal renal failure (creatinine clearance <10 ml/min
Epicephin :dosage must not exceed 2 g daily.
In dialysis patients no additional administration is required following dialysis. Rather, plasma concentrations in these patients should be monitored, as the elimination rate may be reduced. The daily dose should not exceed 2 g in dialysis patients.
In patients with liver damage there is no need to reduce the dosage of Epicephin, provided renal function is not impaired. In concomitant severe renal and hepatic dysfunction, plasma concentrations of ceftriaxones should be determined at regular intervals. Dose adjustments may become necessary, as the elimination rate in these patients may be reduced.
Administration instructions: see Additional Instructions for use and administration.
Epicephin vial contraindications :
Hypersensitivity to the active substance, to other cephalosporins. Previous immediate and/or severe hypersensitivity reaction to a penicillin or to any other beta-lactam medicinal products.
Neonates in the case of:
– Hyperbilirubinemia, because ceftriaxone displacement of bilirubin to serum albumin.
– Parenteral calcium therapy, because precipitation of ceftriaxone calcium salts causes a risk of fatal organ damage to kidneys and lungs.
Premature infants:
because ceftriaxone displacement of bilirubin from its binding to ceftriaxone serum albumin causes a risk of bilirubin encephalopathy.
A small number of cases with fatal outcome in which a crystalline reformer material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving Epicephin and calcium containing solutions. In some of these cases the same infusion line was used for Epicephin and calcium- containing solutions, and in these cases a precipitate was found in the infusion line.
Epicephin vial warnings and precautions:
Special caution is required to determine any other type of previous hypersensitivity reactions to, penicillin or to other beta-lactamase medicinal products because patients hypersensitive to these
medicines may be hypersensitive to Epicephin as well {cross allergy).
As with other cephalosporins, anaphylactic reactions with outcome have been reported, even in patients not known to allergic or previously exposed.
If allergic reactions occur, Epicephin must be immediately and appropriate therapy initiated. Ceftriaxone may prolong prothrombin time. Prothrombin should therefore be checked if vitamin K deficiency is suspected. An immune-mediated hemolytic anemia has been observed patients receiving cephalosporin – class antibiotics. Severe cases of hemolytic anemia, have been reported during treatment in both adults and children a patient develops anemia while on ceftriaxone, the diagnosis cephalosporin – associated anemia should be considered ceftriaxone discontinued until the etiology is determined.
clostridium difficile – associated diarrhea has been reported with use of nearly all antibacterial agents, including Epicephin, may range in severity from mild diarrhea to fatal colitis. with antibacterial agents alters the normal flora of the colon,to overgrowth of C. difficile produces toxins A and S, which contribute to development of CDAD. Hypertoxin-producing strains of C.
cause increased morbidity and mortality, as these infections can refractory to antimicrobial therapy and may CDAD must be considered in all patients who present with following antibiotic use. Careful medical history is necessary in CDAD has been reported to occur up to two months after administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic directed against C.difficile may need to be discontinued,instituted as clinically indicated.
Antiperistaltic drugs are contraindicated in this case.
Blood counts should be performed at regular intervals prolonged treatment. Caution is advised in patients with impaired renal function concomitant treatment with aminoglycosides and diuretics.
Ceftriaxone must not be mixed or administered concurrently calcium- containing solutions, even if the solutions are given in different infusion lines. Cases of fatal reactions due to calcium-ceftriaxone precipitates in lungs and kidneys have been reported in neonates, even when different infusion lines and times of were used for ceftriaxone and the calcium– containing solutions.
For this reason intravenous calcium- containing solutions must be administered to neonates for at least 48 hours after the last of Epicephin (see Contraindications). Cases of intravascular cefrriaxone calcium precipitation concomitant use of ceftriaxone with intravenous calcium containing solutions have not been reported in other age nevertheless, coadministration should be avoided in all patients
Epicephin vial interactions :
No impairment of renal function has been observed after simultaneous administration of large doses of Epicephin , and potent diuretics such as furosemide. No disulfiram – like effect has been demonstrated following administration of Epicephin and ingestion of alcohol. Ceftriaxone does not contain the N-methylthiotetrazole moiety that has been associated with ethanol intolerance and bleeding problems with use of certain other
cephalosporins. Probenecid does not influence the elimination of ceftriaxone. There is no evidence that Epicephin increases the renal toxicity of aminoglycosides. Nevertheless, the two products must be
administered separately (see Incompatibilities). Bacteriostatic drugs can interfere with the bactericidal action of cephalosporins.
Antagonistic effects were observed in an in vitro study of ceftriaxone in combination with chloramphenicol.
Diluents containing calcium (e.g. Ringer’s solution or Hartrnann’s solution) must not be used to reconstitute Epicephin vials or to further dilute a reconstituted vial for intravenous administration because precipitates may form. Calcium ceftriaxone precipitates may also form when Epicephin is mixed with calcium – containing
solutions in the same infusion line. Epicephin must not be administered simultaneously with calcium- containing infusion solutions, including continuous calcium – containing infusions such as in parenteral nutrition via a v-stre. However, in patients other than neonates, Epicephin and calcium – containing solutions may be administered consecutively if the infusion lines are thoroughly flushed between infusions with a compatible solution. In vitro studies using plasma from adults and neonatal cord blood demonstrated that neonates have an increased risk of calcium
ceftriaxone precipitation (see Dosage and administration and contraindications. There are no reports of interactions between ceftriaxone and oral calcium- containing products or between intramuscular ceftriaxone and calcium- containing products (Intravenous or oral).
Epicephin vial pregnancy and lactation :
Pregnancy: Ceftriaxone crosses the placental barrier (see Pharmacokinetics / Distribution). No controlled clinical studies are available. Although no evidence of teratogenicity was detected in the relevant preclinical studies, Epicephin should only be used in pregnancy, particularly in the first three months, if there is an indication for its use.
Lactation: As ceftriaxone is excreted – in low
concentrations in breast milk, the product should not be used by nursing mothers.
Where treatment is absolutely essential, breastfeeding should be stopped.
Epicephin vial effects on ability to drive and use machines:
No relevant studies have been performed.
Because of possible side effects such as dizziness, the ability to drive motor vehicles and operate machines may be impaired by Epicephin.
Epicephin vial undesirable effects :
The following side effects, which subsided either spontaneously or after withdrawal of the drug, have been observed during the use of Epicephin.
Infections:
Rare: Mycosis of the genital tract, superinfection with non-susceptible organisms.
Epicephin vial blood and lymphatic system:
Common: Eosinophilia, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, prolongation of prothrombin time.
Rare: Elevation of serum creatinine.
Very rare: Coagulation disorders.
Very rarely, cases of agranulocytosis have been observed, mostly following a total dose of 20 g or more.
Blood counts should be performed at regular intervals during prolonged treatment. Slight prolongation of prothrombin time has been reported.
Epicephin vial gastrointestinal disturbances:
Common: Loose stools / diarrhea, nausea, vomiting, stomatitis, glossitis.
Rare: Pancreatitis, possibly due to bile duct obstruction. Most of the patients concerned had risk factors for cholestasts and biliary sludge,e.g. preceding major surgery, serious disease or total parenteral nutrition. The possibility that Epicepbin may act as a trigger or cofactor in the formation of gallbladder precipitates cannot be ruled out.
Very rare: Pseudomembranous enterocolitis.
Liver and gallbladder:
Very common: Symptomatic precipitation of ceftriaxone calcium salt in the gallbladder of children, reversible cholelithiasis in children. This disorder occurs rarely in adults (see Warnings and Precautions}.
Common: Increase in serum liver enzymes.
Skin:
Common: Rash, allergic dermatitis, pruritus, urticaria, edema.
Very rare: Severe skin reactions (erythema multiforme, Stevens Johnson syndrome or toxic epidermal necrolysis).
Kidneys and urinary tract:
Rare: Oliguria.
Very rare: Renal precipitates have been reported, mostly in children aged over 3 years who were treated with either high daily doses (e.g. 80 mg/kg/day) or total doses in excess of 10 g and who had additional risk factors (e.g. reduced fluid intake, confinement to bed,
etc.). This side effect mayor may not give rise to clinical manifestations, can lead to renal failure, and is reversible upon discontinuation of Epicephin.
Epicephin vial general disturbances and administration site reactions:
Rare: Headache, dizziness, fever, chills. Anaphylactic or anaphylactoid reactions.
Vein wall inflammatory reactions after i.v, administration. These may be minimized by slow (2 – 4 minutes) injection of the substance.
Intramuscular injection without lidocaine solution is painful.

Epicephin vial Interactions with calcium:
Two in vitro studies, one using adult plasma and the other neonatal plasma from umbilical cord blood, have been carried out to assess
tnteractlon of ceftriaxone and calcium. Ceftriaxone concentrations up to 1 mm (in excess of concentrations achieved in vivo following administration of 2 grams ceftriaxone infused over 30 minutes)
were used in combination with calcium concentrations up to 12 mm (48 mg/dl).
Recovery of ceftriaxone from plasma was reduced with calcium concentrations of 6 mM (24 mg/dl) or higher in adult plasma or 4 mm (16 mg/dl) or higher in neonatal plasma. This may be reflective of calcium ceftriaxone precipitation.
A small number of cases with fatal outcome in which a crystalline material was observed in the lungs and kidneys at autopsy have beenreponed in neonates receiving Epicephin and calcium – containing solutions. In some of these cases the same infusion line
was used for Epicephin and calcium- containing solutions, and in some a precipitate was found in the Infusion line. At least one fatality has been reported in a neonate to whom Epicephin and calcium-containing solutions were administered at different time points and via different infusion lines; no crystalline material was observed at autopsy in this neonate.
There have been no similar reports in patients other than neonates (see Warnings and precautions).
Epicephin vial overdosage :
Excessive plasma concentrations of ceftriaxone cannot be reduced by hemodialysis or peritoneal dialysis. Symptomatic measures are recommended for the treatment of patients following overdosage.
Epicephin vial properties and effects :
Mechanism of action / Pharmacodynamics;
The bactericidal efficacy of ceftriaxone results from inhibition of cell wall synthesis. Ceftriaxone exerts broad-spectrum activity in vitro against grarm- negative and gram- positive microorganisms.
Ceftriaxone is highly stable to most beta lactamases – both peniclllinases and cephalosporinases of grarm- positive and
grarm-negative bacteria.
Ceftriaxone is usually active against the following microorganisms in vitro and in clinical infections (see Indications)
Epicephin vial package :
Packs for IM injection:
Epicephin 500 mg vial: 1 vial + 1 ampoule (2 ml of 1% lidocaine solution).
Epicephin 1 gm vial: 1 vial + 1 ampoule (3.5 ml of 1% lidocaine solution).
Packs for IV injection:
Epicephin 500 mg vial: 1 vial + 1 ampoule (5 ml) of sterile water for injection.
Epicepbln 1 gm vial: 1 vial + 1 ampoule (10 ml of sterile water for injection.
Packs for IV infusion:
Epicephin 2 gm vial: 1 vial + 1 ampoule (10 ml) of sterile water for injection.
Produced by :
EGYPTIAN INT. PHARMACEUTICAL INDUSTRIES CO.
E.I. P.I. CO.
10th OF RAMADAN CITY, INDUSTRIAL AREA er, P.O. BOX: 149 TENTH, EGYPT