Epicephin Vial
Composition :
Active ingredient: ceftrtaxone (as the disodium salt). Epicepbln contains approximately 83 mg {3.6 mEq) of sodium per gram of cefrriaxone.
Pharmaceutical form and quantity of active substance per
unit: 500 mg t.v.
Dry substance: ceftriaxone 500 mg as dtsodrurn ceftrtaxone per vial.
Solvent: water for injection 5 ml.
500 mg I.m.
Dry substance: ceftrtaxone 500 rng as disodiurn ceftriaxone per vial.
Solvent: lidocaine hydrochloride 20 mg, water q.s. 2 rnl of solution.
1 g I.m.
Dry substance: cefrrtaxone 1 g as disodium ceftriaxone per vial.
Solvent: water for injection 10 ml. 1 g i.m.
Dry substance: ceftnaxone 1 g as dtsodturn ceftrtaxone per vial.
Solvent: lidocaine hydrochloride 35 mg, water q.s. 3.5 ml of
so/urion. 2 g I.m.
Dry substance: ceftrtaxone 2 9 as dlsodlum ceftnaxone per 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 throar infections;
– abdominal infections (peruomus, infections of (he biliary and
gasuointestinal tracts);
– renal and urinary tract infections;
infections or the genual organs, mdudmg gonorrhea;
– infections of the bones, [otnts. soft tissue and skin, and wound
Infections; mrecnons in patients with Impaired immune response;
– meningitis
– disseminated Lyme borreliosis (stages 11 and lll).
Perioperative prophylaxis of infections in operations on the
qastrotntesnnal tract, biliary tract and urogenital tract and In
qyneccloqtcal 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 10 prevent Increased antibiotic resistance.
Dosage and Administration :
Dosage:
Adults and children over 12 years: The usual dosage is 1 – 2 g of
Epicephin: once dally {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 115 days to 12 years): A daily dose of 20 – 80
For children with abodyweight of 50 kg or more, the usual adult
dosage should be used .
InuavenoUs 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 or 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 zae
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 meningitldts 4 days
Haemophilus tnnuenzae 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
far 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 nsl
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. In
cclorectal surgery, simultaneous administration of EpicephlD and a
5 rutrotrrudazole. e.q. ornidazale, has proven effective. IdiS group]
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 n~t impaired. In concomitant severe renal and nepanc dysfunction, plasma concentrations of ceftJiaxone 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
Contraindications :
Hypersensitivity to the active Substance, to other cephalosportns or aboratory to any of the exctpfents. Previous immediate and/or severe hypersensitivity reaction to a penicillin or to any other beta-lactam medicinal products.
Neonates in the case of:
– hyperbtlirubtnerrua, because ceftrtaxone displacement of bilirubin
to serum albumin causes a risk of bilirubin
– parenteral calcium therapy, because precipitation of ceftnaxone
calcium salts causes a risk of fatal organ damage to kidneys and lungs.
Premature infants:
because ceftriaxone displacement of bilirubin from its binding to ceftriaxo serum albumin causes a risk of bilirubin encephalopathy.
A small number of cases with fatal outcome in which a crystalline recornmer material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving Epicepbin and calciumcontaining solutions. In someoethese cases the same infusion line was used for Eplcephin and calcium- containing solunons, and in these sped some a precipitate was found in the infusion line. At least one fatality ·has been reponed in a to whom Epicephin and
calcium-containing soluttons lwere administe~.ed. at different time
points and via different infusion lines; no crystalline material was
observed at autopsy in this neonate. here have been no similar
reports in patients other than neonates (see Undesirable effects). It.
Warnings and precautions:
Special caution is required to determine any other type of previous
hypersenstttvity reactions to, penicillin or to other beta-lactarn reus
medicinal products because patients hypersensitive to these
medicines may be hypersensitive to Epicephln as well {cross allergy).
As with other cephalosportns, anaphylactic reactions with outcome have been reported, even in patients not known to allergic or previously exposed.
If allergic reactions occur, EpicephiD 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
Epluphin. Severe cases of hemolytic anemia, including have been reponed 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 etio!ogy is determined. clostridium difficlle – associated diarrhea has been reporn with use of nearly all annbactenal agents, including Epicephin, may range in everiry from mild diarrhea to fatal colitis. with antibactenal agents alters the normal flora of the colon,to overgrowth of C. difficile produces toxins A and S, which contribute to development of CDAD. Hypertoxtn-productnq strains of C.
cause increased morbidity and mortality, as these infections can
refractory to antimicrobial therapy and may CDAD must be considered in all panents who present withfollowing antibiotic use. Careful medical history 1S necessary sin CDAD has been reported to occur up to two months after administration or anttbactertal 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 this case.
During long-term use of Epicephin,A1on – susceptible microorga
“tsms may become difficult to control. Close patient supervtslo
therefore essennal. Appropriate measures must be taken
superinfection occurs during treatment.
Shadows that mq, be mistaken for gallstones have been detected
ultrasound scans of the gallbladder. Such shadows generally COn!
of precipitates of the caldurn salt of ceftrtaxone. These precipital
usually occur following doses higher than the recommended
The shadows disappear on completion or dtsconnnuanon
Eplcepb1D therapy.
Rarely, these findings have been associated with symptoms.
symptomatic cases conservative, nonsurgical management
recommended. Discontinuation of EpicephJn in symptomatic cas
should be at the discretion of the doctor.
Rare cases of pancreatitis possibly due to cholestasts have be
reported in patients treated with EplcephiD. At interview most of I
patients concerned were found to have risk factors for cholesta
and biliary sludge, e.g. extensive previous treatment, serious disec
or total parenteral nutrition. The posstbthry that precipitates due to EpicepblD. may act as triggers or cofacl
cannot be ruled out.
Ceftriaxone can displace bilirubin from its binding to Treatment of hyperbilirubinemic neonates is theref contraindicated [see Contratndtcanons]. 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 different infusion lines. Cases of fatal reactions due to cal
ceftriaxone precipitates in lungs and kidneys have been neonates, even when different infusion lines and times of were used for ceftnaxone and the caldurn – containing solutld
For this reason intravenous calcium- containing solutions 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 caloum containing solutions have not been reported in other age nevertheless, coadministration should be avoided in all patients
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 followinq administration of Eplcephin and ingestion of alcohol. Ceftnaxone 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 Eplcephln increases the renal toxicity of aminoglycosides. Nevertheless, the rwo products must be
administered separately (see Incompatibilities). Bacteriostatic drugs can interfere with the bactericidal action of cephalosportns.
Antagonistic effects were observed in an in vitro study of ceftrtaxone 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 ceftrtaxone precipitates may also form when Epiccphln is mixed with calcium – containing
solutions in the same Infusion line. EpicepbiD 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, EpiccpbJn 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
Contratndlcanonsl. There are no reports of interactions between ceftrtaxone and oral calcium- containing products or between intramuscular ceftnaxone and calctum- containing products [Intravenous or oral).
Pregnancy and lactation :
Pregnancy: Ceftrlaxone 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 a
indication for its use.
Lactation: As ceftriaxone is excreted – albeit in lowconcentrations
in breast milk, the product should not be used by nursing mothers.
Where treatment is absolutely essential, breastfeeding should be
stepped.
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 Epiccpbia.
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.
Blood and lymphatic system:
Common: Eosinophilia, leukopenia, granulocytopenia, hernolync
anemia, thrombocytopenia, prolongation of prothrombin time.
Rare: Elevation of serum creatinine.
Very rare: Coagulation disorders.
Very rarely, cases of agranulocytosis « SOO/mm3) 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.
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.
Uver and gallbladder:
Very common: Symptomatic precipitation of ceftnaxone 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 (AST [SCOT], ALT [SCPT), alkaline phosphatase}.
Skin:
Common: Rash, allergic dermatitis, pruritus, urticaria, edema.
Very rare: Severe skin reactions (erythema multiforme, Stevens •
Johnson syndrome or LyeU’s syndrome / 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 EpicephiD.
General disturbances and administration site reactions:
Rare: Headache, dizziness, fever, chills. Anaphylactic or anaphylac-
toid 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.
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 ceftrtaxone 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
been reponed in neonates receiving Epicephiu 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 caldurn . containing solutions were administered at different time points and vi 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).
Overdosage :
Excessive plasma concentrations of ceftriaxone cannot be reduced
by hernodtalysis or peritoneal dialysis. Symptomatic measures are
recommended for the treatment of patients following overdosage.
Properties and effects :
Mechanism of action / Pharmacodynamics;
The bactericidal efficacy of cefmaxone results from inhibition of cell
wall synthesis. Ceftriaxone exerts broad • spectrum activity in vitro
against qrarn- negative and qrarn- positive microorganisms.
Ceftrtaxone is- highly stable to most j3 lactamases – both peniclllinases and cephalosporinases of qrarn- positive and
qrarn-neqattve bacteria.
Ceftrtaxone is usually active against the following microorganisms in
vitro and in clinical infections (see Indications)
Package :
Packs for IM injection:
Epkephin 500 mg vial: I 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:
Epfcephib 500 mg vial: 1 vial + 1 ampoule (5 ml] of srenle water
for injection. u-ol
Epicepbln 1 gm viaJ: ] vial + 1 ampoule (10 ml of sterile water for
injection.
Packs (or IV infusion:
Epicephln 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
