Ceftriaxone Sodium Forgram 500 mg and 1 g Powder for Injection Intramuscular / Intravenous Antibacterial --500mgor 1g PRODUCTDESCRIPTION Ceftianone sodium i.a white to yellowish white powder contained ina colaress vial, sterile and pyroger-free. Aner reconstitution, the Color of solution ranges from paleto yellow toamber dependingonthelengthof storage, concentration anddiluent used. Thi product comes with a § mL and 10 mL sterle water for injection as diluent forthe 500 mg and 19 ceftriaxone powder for infection, respectively GLINIGAL PHARMACOLOGY PHARMACODYNAMICS Ceftianone is.a third generation cephalosporin with antibacterial activty similar to peniclins, carbacephems and cephamycins. Ceftrisnone exerts its bactericidal activity by interfering with the bacterial cell wal symthesis. binds to speci peniciin-binding proteins responsible for the synthesis of peptidoglycan, a heteropolymerc structure that gives the cell wall &s mechanical stability. ‘The final stage of peptidoglycan synthesis volves completion ofthe cross-linking ofthe terminal glycine recidue of the pentagheine brdaeio eft osc oth petperie. The trancpeptidace enzyme that catalyzes ths step ic inhibited by cephalogponns. ‘Asa result the bacterial coll wall is weakened, the cell swels and then ruptures. ANTIMICROBIAL SPECTRUM OF ACTIVITY a calooaceicus "Moraxelia calartals (ncoang beta lactamase verobacter aerogenes produchg trains) chi cot Neisseria gonorrhoeae (inckuing peniilinace- sinfuenzae (cluding ampiciin-resistant ‘and nonpenicilinase-producing strains) betaJactamase producing strains) ‘Neisseria meningitis joxytoca Proteus vulgaris Klebsiella preumonive Serratia marcescens ‘Aerobic Gram Positive ‘Anaerobes ‘Staphylococcus aureus (induding peniclinase-producng Bacteroides fragits strains) Ctostrignam sop. Staphylococcus epidermis: Peptostreptococcus spp. Streptococcus pneumoniae ‘Sepocoecus pyogenes Viridans group streptococci Ceftriaxone is also active against manystairs of Pseudomonas aeruginosa, Ceftrianone has been shown tolbe active in vo against most strains of the folowing organism; however, the cinical significance of these datas unknown: “Aerobic Gram-Negative Girobacter reunct Providencia spp. (ncuding Prowidenciaretiger) | Salmonea spp. (including Salmonella typhi) Nethicilin-resistant staphylococci areresistant ta vephalosphorins, including ceftriaxone. Methicili resistant staphyfococe’ are resistant to cephaloceorins, including ceftriaxone. Most strains of Group D streptucoce! and enterococe, ¢.9., Enterasoccus{ Streptocoocus) faecal, are resistant Most strains of Clostridum dice are resistantto ceftriaxone. Ini suggested to.cany out senastvty tests, PHARMACOKINETICS Ceftianone isnot appreciably absorbed from the gastrointestinal tract and must be administered parenterally. ‘After intramuscular (IM) administration of a single 500 mg to 1 g.cefviawone dose in healhy aduts, the drug appears to be completely absorbed, and peak serum concentrations (C.,,) are attained 15-4 hours after the dose. In a study in heathy adus given.a sngle-f IM dose of cefriaxone, mean serum concentrations of the drug were 28.9, 43.7,€2.3, 83.2,40.6,36.5, and7.8 mogiml at 0.25, 0.5.1, 2.6, 112, and24hours respectively, ater the dose, ‘After a 30-minute intravenous (IV) infusion of a single 1 9 dose of ceftriaxone in healthy adults, mean C,,, of the drug at completion of infusion were 123.2-150.7 mogiml. and mean serum concentrations at 1, 2,6, 12, and 24 hours afer start of infusion were 109 5-111, 60.8-88.2, 33-52-5, 20.2:28.1, and 4.6-9.3 mogiml. respectively. In mtiple dose studies in heathy adults given 500 ng to 2q doses of ceftriaxone administered every 12 0r24 hours by IM injection or V infusion over 30 minutes, serum concentratens cf the drug at steady state on the faurth day of therapy were 15-36% higher than serum concentrations attained with ingle doses. ‘The volume of dstrbution of ceraxoneis dose denendentand rangesfromS.8-13.5L inhealhy acts. Ceftriaxone is widely distributed in body tissues and fds including the galbledder, hangs, bone, heart, bile, prostate adenoma tissue, erine tissue, atial appendage, sputum, tears, middle ear fad, and plewral, peroneal, synovil, asclic, and bister fide, Only low ‘concentrations of the drug are distributed into aqueous humoe after IV or ih administration. Ceftriaxone diffuses into the cerebrospinal fluid (CSF) afte IM or IV administration; the CSF concentrations ofthe drug are higher in patents wit inflamed meninges than in those with unindamied meringes. The crug is 93-96% bound at a concentration ess than 70 mogimlL. It crosses the placenta andis dstriaded intoamnit fu andinto makin low concentrations. ‘The degree of protein binding of ceftriaxone & concentration-dependent and decreases noninearly with increasing drag concentrations. Cofrianone binds mainly to albumin. Proten binding of ceftriaxone is lower in neonates and chidren compared with adults because of decreased plasma albumin concentrationsin this age group. Its also less protein bound in patents with renal rhepatic impairment 2s a result of decreased plasma albumin concentrations or césplacement from protein binding sites: by blirubin and other endogenous ‘compounds thatmay sccumulate, Plasma ceftrianone concentrations decline na biphasic manner. The dietrbution hat-e (t.,)and elimination hate) in ads with ‘normal renal andhepaticfuncton are 0:12-0 7 and§ 4-10 Shours, respectively. ‘About 40-85% ofa doce of oefviaxone is excreted unchanged in the urine, mainly by glomerular ration; the remainder is excreted inthe bileandis ultimately foundinthe feces as unchanged drug and microbialogicallyinactve metaboites. ‘Serum clearance of cefriaxone is dose-dependent and ranges from 97-25 mLiminute in healthy aduts. The serum of oeftraxone islonger in neonates than in older children and adits. The average eliinationt,q0! the drugis 4-7 7 houre in chicken 1.5 monihe to 16 years old and is similar to that reported in adults. The elimination tq of cefiiaxone is only sightly prolonged in patients wih moderately impaired renal functon ranging ftom 10-16 hours in adults with creatinine clearance of 5.73 mLimin.te. Studies in patients with hepatic impairment indicate that the pharmacokmetics (PK) of ceftriaxone are not generally altered in these patients. Ceftriaxone is not removed by hemodialysis cr pentoneal dialyis. INDICATIONS. “> Forthe treatment of the folowing infections due to susceptble organisms: * Lower respiratory tract infections including pneumonia + Acuteacterialttic media + Skinandskinstructureinfections * Urinary tractinfectons (complicated and uncomplicated) Uncomelicated gonorrhea (senvicaliuretral, pharyngeal andrecal) Petviciniammatory disease Bacterial septicemia Bone and jointinfecsions: Inza-abdorinal infections (pentonite, infections ofthe biary and gastointestnaltracts) + As perioperative prophylaxis to reduce the incidence of postoperative infections in patients undergoing contaminated or potently contaminated surgical procedures (e.g, vaginal or abdominal hysterectomy or cholecystectomy for chronic calculous: cholecystis in high risk patients such ac those > 70 years old, wih acute cholecyeti, obstructive jaundice or common bile duct stones) and in patients for whom infection at the operative site would pose a cenous risk (e.g., during coronary artery bypass: curgery). signe of post-curgeal infection should appear, specimens for culture should be ablained for identicaion of the causative organniomes co that appropriate therapy may be nstiuted, DOSAGE AND MODE OF ADMINISTRATION: * Donotuse dilvents containing calcium, such as Ringer's solution or Hartmann’s solution to reconstitute ceftriaxone. ‘This can result particulate formation. * Ceftriaxone maybe administered IV or IM after reconstitution. Doses above 50 mg/kg shouldbe given by [Vinfusion only. * Direct IV injectionis administered over a period of2 to 4 minutes, + Winfusion i administered over a petiod of 30 minutes Concentratons between 10 mgimL and 40 mg/ml are recommended, ‘however, lower concentrations may be used. * Dosage and route of adminsstration should be determined by the severity of infection, susceptibility of the causative organisms, andthe patient's conditon. The IV route is preferablein patents with sepboemiaor other severe orlife.threatening mfechons. + Dosage of ceftriaxone saiumis expressedin terms of ceftriaxone andisidentialforIMandV administration UsualAdultDose: 1.2 grams. given once daly orinequally divided doses tuice daly, depending on the ype and ceverityofinlection. Maximum AdultDose:4giday Recommended Dose for Specific Infection in Adults Infection ‘Adult Dose [Lower respiratory tract infections including pheumoria 1 IV every 120° 24 hours in conjunction with other ant- Incomphcated gonorrhea mg IM Single dose [Pelvic milarmmatory disease [250 mg IM Single doce followed by oral daxycycline 100 mg [twice daily for 14 days with or without oral metronidazole 500 mg [ice day [Surgical Prophytaxis i gIV Single dose ¥to 2 hours before surgery [Cholecystectomy 1-29 IV Single dose % to 2 hours before surgery. Meningitis PglVevery 12 hours * IV ceftriaxone has been shown tobe effective forthe treatment of meningitis in some aduts when administered at a dose of 50-100 mg/kg (maximum dose 4 9) once daily. While 7 days of ceftriaxone therapy may be adequate for the treatment of uncomplicated meningtis caused by susceptible Haemophilus influenzae or Neisseria meningiidis, t least 10-14 days of therapy is suggested for complicated cases or meningits caused by Strepiocoocus pneumoniae and atleast 21 days of therapy is recommended for meningitis causedby susceptible Entercbacteriaceae (Escherichia cal, Klebsieds). [*Neomates (up to 14 dave) infants and Chitdren (15 days to 12 yeare old) potential sk of bilrubin encephalopathy. Recommended Dose for Specific Infectionin Neonates and Children <12 years old Infection Pediatrie Dose [Skin and skin sbucture infections 75 mgjkg body weight gen once daly or in equally dvided every 12 hows, mum dose: 2 g'say bacterial obs media Tigikg bodyweight (not to exceed 11g) IM Single Dose [Serious infectons (other than meningitst) LTS inf boty weigey sven in equal cided doves { ium dose: 2 glday [Meningits 1100 mgkg"body weight given once daly or in equally divided ‘every 12 hours for 7-21 days [Maximum dose: 4 giday weighing < 50 ig with uncompbcaled gonccoccal vivowagiats, ceniche, urethritis, epididymis, phanygjie, o procts be given a single 125mg IM doce of cefriaxone. Duration of Treatment * Usual duration oftherapy isto 14 days, but complicated infections mayrequir longer treatment. * Formost infections, except gonorrhea, contnue therapy fr atleast 4610 72 hows after the patient becomes asymplomatic or evidence ofbacteral eradication has been cktained. + When reatinginfectons caused by Streptococcus pyogenes, continue therapy or atleast 10:days. Dosage in Renal and Hepatic Impairment No dosage adjustment is required in patients with impaired renal funcfon. However, monitor blood levels in patients with severe renal impairment (creatnine dearance < 10 mLmin) and in patients with both renal and hepatic dysfunctions. if evidence of accumulation of ceffraxone occurs, dot age shouldbe decreased accordingly, Dose in adits with both hepsticand significant renalimpairmént should not exceed 2g daily unless cerum concentrations of the drug are clocely monitored, Since cefsiavone is not removed by hemodialysis, supplemental doses ofthe drug are unnecessary during or after dalysis. (Or,25 prescribed bya physician. Directions for Parenteral Administration ForiMinjection * Dissolve cefrianone 500 mg in 1.8 mL and oeffiaxone 1 9 powder for injection in 3.6 mL 1% Lidocaine solution to provide ‘solutions cantaining approximately 250 mgm + Administerbyydeep intraglutea injection. * Never administer ceftriaxone and lidocaine solutionintravenously. * Itisreccemmendedthat not more than Igbeinjectedat angle site. Forbireet lVinjection + Dissolve ceftianone'5001mg in B ml and ceftriaxone gpowderfor injection in 6 mL Sterile Water for Injection. ForlVinfusion * Reconstiute ceftriaxone 500 mg 4.8 mLand ceftriaxone 1 g powder for injection in 9.6 mL Sterke Water for injection. After reconstitution, the soluson contains approxcmately 100 mgimL of cefmiaxone. + Dilute the reoonstiuted solution tothe desired concentration wih any ofthe foloming calcium-ee infusion solutions: Sodium ‘Chloride 0:94 solution, Sodium Chloride 0.45% in Dextrose 2.5% sohaion, Dextrose 5% soluion, Dextrose 10% solution, LLevuiose 5% soluion, Dextran 6%in Dextrose solution, and Sterile Water for Iejecon. “> Prior to- administration, parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and cantainer penne. “> Shake the reconstituted solution before use, + Observe strict aseptic technique when drawing up the cantents ofthe vial. Ifcontaminated, it hasthe potentiate became.a source oF infecfiontopatients. Compatibility, Storage and'Stabilty * Aber action calianere suis rin phil nd hail aby or eho eon lope oro 2 at2"C 108% + Due to possible incompatibility, cefrianone solufons should not be physically mixed or piggybacked into solutions containing ‘ther antiricrobial drugs orinto diuents oer than those listed above, + Discard any unused solution after penods sated CONTRAINDIGATIONS “* Hypersensitivity to cephalesphorins or other component ofthe product “+ Hypersensitivity to lidocaine solution (in case of IM injection) ~ Hyperbdirubinericjaundied neonates, especially prematures + Neonates (5 28 days of age) who require (ot are expected to require) treatment with calciurr-containing IV solutions, inchuding continuous calcium-containing infusions uch as parenteral nurtion because ofthe risk of precipitation of cefrantone-caloum [see Warnings and Precautions, Undesirable Effects] WARNINGS AND PRECAUTIONS: * Ceftriaxone should not be mixed or administered simultaneously with calcium-containing WV solutions, including continuous, calcium-containing infusions such as parenteral nutrition via.a Y-site because precipitation of ceftriaxone-calcium can ‘occur. However, in patients other than neonates, cefyiaxone and calcium-containing solutions may be administered sequentially, ‘Provided the infusion lines are thoroughly flushed between infusions witha compatible fd, * In vino studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of ‘precipitation of ceftiaxone-calcium, (Cases of fatal reactions with calcium-ceffriaxone precipitates in lung and kidneys.in both termand premature neonates have been described. In some cases, the infusion lines and times of administration of ceftriaxone and ealcium-containing solutions differed. ‘Athough, there have heen no reports to date of intravascular or pulmonary cefiaxone-calcium precipitates in patents other than neonates treated with ceftriaxone and calciurn-containing solutions, caution is nevertheless warranted duringll treatment. No data are availatle on potential interaction between cefiriaxone.and oral calcium-containing products or interaction between IM ceftriaxone and calcium-containingproducts (IV ororal). * Careful inquiry should be made conceming previous hypersensitivity to cephalosporins, penicillins, or other drugs before initiating therapy with ceftriaxone. ceftriaxone is given to penicilin-sensitive patients, caution should be exercised since partial cross-allergenicity among beta lactams antibiotics has been clearly documented. fan allergic reaction to ceftriaxone ‘occurs, discontinue treatment withthe drug. Serious aoute hypersensitviy reactions may require treatment with epinephrine.and other emergency measures including oxygen, Mv fluids and IV antihistamines, corticosteroids, pressor amines, and airway managementas clinically indicated. * Geffriaxone should not be administered in patients with a history of cephalosporin-associated hemolytic anemia since the recurrence af hemolysisis much more severe. Animrmune-mediated hemolytic anemia has been abservedinpatients receiving cephalosporin dass antbiatics, including o=friaxone, ‘Severe cages of hemolytic anemia, including falalies, have been reported in both adults and chilren. Ia patient develops anemia anyimme during, of within 2-3 weeks subsequent to the administration of ceftriaxone, the diagnosis ofa cephalosporin-associsted ‘anemiashouldke considered and ceftriaxone dicoontinzed unil the efiologyis detenrined. Periodic monitoring for signs and symptoms of hemolyfc anemia, including measurement of hematological parameters or drug- induced antleody testing is recommended in patients during prolonged or frequent coursesof cefriaxone, * Ceftriaxone should be discontinued in patients who develop signs and symptoms suggestive of gallbladder disease, including sonographic abnormalities. ‘There have been reports of sonographic abnormalities in the gallbladder of patents treated with ceftriaxone [see Undesirable [Effects], some of these patients also had symptoms of gallbladder disease. The condition appears tobe transient and reversible upon ‘discontinuation of cefriaxone.andinstiution of conservative management. ‘Since ceftriaxone can preciptat in the gallbladder, the drug should le used with caution injpatents wih preexisting disease of the \galblader bilrytrac, iver, or pancreas, andifthe drugs used in such patients that serial abdominal utrasonography be performed during therapy. * Clostridium dificile associated diathea (CDAD) and colitis has been reported with use of nearly all antibacterial agents, including ‘cefiiaxone, and may range in severity from mid diarrhea to atl cals tis important o consider this siagnos'sin patents who present with diamhea, oF symptoms of colts, pseudomembrancus colitis, toc megacolon, or perforaton of colon subsequent to the administration of any antibacterial agents. CDAD has been reported to occur over fwo months afer the adminsstration of antibacterial agents. * As with other broad-speciram aniibitice, cefriaxone should be given with caution in individuals with a history of gastrointestinal disease, particularly codts. Cephalosporinshave been associated with the developmentof seizures, particularly inpatients with renal impairment, in whom dosage ofthe drugwas not reduced. * Cephalosporins maybe associated with a fallin prothrombin activity Patients who are at riskare those withrenal ar hepatic impairment ‘poor nutritional state, as well as patient receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time shouldbe monitoredin patients atriskand exogenous Vitamin Kadministered as indicated * Prescribing ceftriaxone in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide beneft io the patient andincreaces theriskof developmentof drug-resistantbacteria, * Use of ceffriaxone may result in overgrowth of nonsusceptible organisms, especially Candida, enterococci, Bacteroides fragis, ot Pseudomonas aeruginosa. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Considering the maximum duration of treatment andithe lass of compound, carcinogenicity studies with ceftriaxone in animals have not een performed. The maximum duration of animal toxicity studies was 6morths. Mutagenesis: In viro studies using microbial (.e., Ames test) or mammalian cell (e., human lymphoblasts) systems have not shown ‘efriaxone to be mutagenic. Spectficstudies to determine the carcinogenic potential of cefiawone have nat been performnedto date, arid animal stadieshave been performed toa maximum duration of only months. Impairment of Fertility: Cefriaxone produced no impairment of fertty when given intravenously to rats at daily doses up to S86 mgixgiday, approximately 20 times the recommended nical dose of2 g/day, Effects on Ability to Drive and Use Machines: Nostudies onthe effects on the ability1o dive and use machines have been performed. However, undesirable effects may occur (eg, dizziness), which may influence the ably to drive and use machines. Patients should be cautious when driving or operating machinery. INTERACTIONS WITH OTHER MEDICAMENTS ‘Alcohol A possible disulfram-ike reaction may ovcur when cefiriaxone is taken vith alcohol. [aminoglycosides (eg, amikacin, gentamicin andtobramycin) |The antibacterial achvly of cefiraxone and aminoglycosides (eg, amikacin, gentamicin and tobramycin) may be synergistic against some strains of Enterobacteraceae and some strains of INoimpairment of renal function has been observed after concomitant adrinistration of ceftriaxone and potent diureics, (Concomitant we with oral anticoagulants may increase the ani- witamin K effect and the risk of bleeding Its recommended that ine Interanational Normalised Rao (INR) is monitored frequent and the dose of the vitamin K drug be adjusted accordingly, both during and after treatment Probenecid [Concomitant adrrinisiration of oral probenecid 500 mg daly does not affect the PK of cefiaxone. However, 110 2 gram dases of [probenecid may result in about 30% increase in ceftriaxone: serum clearance and about 20% decrease in ceftianone elimination ty Trovaffoxacin [Akthough the cinical importance is unclear, resuts of an in vitro) study indicate thatthe combination of ceftriaxone and trovafloxacin is synergistic against both penicilin-cusceptible and penicllin,| resistant Streptococcus pneumoniae, including some strains that are resistant to ceftriaxone alone [AS-with ather anibiocs, cefaxone may affect the gut flora, leading to lower estrogen reabsorption and reduced effcacy of combined oral estrogen|pragesterone contraceptives. Therefore, altemative non-hormonal methods of contraception are recommended (Oral Anticoagulants: Interference with Laboratory Tests As with most cephalosporins, ceftriaxone interferes with winary glucose test using cupic sulfate (Benedict's solution, Clnitest’) Itis recommended touse glucose oxidase methods. * false positive Coombe’testhas been rarely observedin patients treated with ceftriaxone. As wth other antbictics, ceftriaxone may resultinfalse-positve tests for galactosemia + Inone in iro study, high concentrations of cefiriaxone (50 megimL or greater) cused falsely elevated serum creatinine values when a manual method was used. Cther studies indicated that ceiiaxone does not interfere with automated methods for Cetermining serum or urinary creatinine concentration. ‘STATEMENT ON USAGE FOR HIGH RISK GROUPS Pregnancy: (Pregnancy Category) Reproduction studies in ice andrats- using dosages up to 20 times the usualhuman dosage have notrevealed evidence of embryotoxiiy, etutonicity or teratogenicity. In primates, no embryotoxciy or teratogenicity was demonstrated at a dose approximately 3 times the usual human dosage. Since there are no adequate and well conivolled studies to date using ceftriaxone in pregnant women, cefiaxone should only be used during pregnancy when clearly needed and when the potential benefits sty hepotental risks. Lactation: Low concentrations of ceftranane ae excreted in human milk. Ceftriaxone should be used with caution in breastfeeding women. Children: The safety and efficacy of ceftriaxone in neonates, infants and pediatric patents have been established. As with some other cephalosporins, in vitro studies have shown that ceftriaxone, at therapeutic concentrations, can displace biliuin from its binding to serum albumin andbilrubin encephalopathy can possibly developin these patients see Contraindications]. Elderly: Nodosage modificationis necessaryin older patients provided that renal and hepatictunctions are satisfactory. UNDESIRABLE EFFECTS Ceftrawone is generally wel-tolerated. The following adverse effects (AES) were considered to be either relatedta ceffraxone therapy or wereof uncertain etiology: General / Local Reactions: Eochymosis, induraton, pain and tendemess at the injection ste after IM administration (pain or IM injection is usually mild andless frequent when the drug ssadrinsstered in teile 1% Lidocaine solution); phlebitisand pain tthe injection Site after NV administration which can be minimizedey Siow jection over at least 2-4 minutes, pyrexia, rigors, thrombophlebitis ighiness andwarnth Central Nervous System’ Ataxia, convulsions, dizziness, headacheand paresthesia Dermatologic / Hypersensitivity Reactions: Acute generalized exanthematous pustulosis (AGEP), allergic dermatitis, allergic skin reactions such as maculopapular rach or exanthema, chills, edema, fever, isolated cases of severe ovianeous adverse reaciions (erythema multforme, Stevens-Johnsan Syndrome, or Lyells sydrometoxc epidermal necrolysis), pruttus; rash (erythematous, \wticaral); superinfection'secondary infections with yeast fungior resistant organisms anduurticaria Gastrointestinal Abdominal pain, bikary lithiasis, CDAD and colifs/pseudomembranous colts symptoms, colts, dzerhea/loose stools, dysgeusia, dyspepsia, flatulence gallbladder sludge, gastic pain, glossiis, nausea, pancresttis (possibly secondary to biliary struction), stomatitis and vomiting Genitourinary: Erythrocytura, glycosuria, gertal mycosis, hematuria, increased concentrations af blood urea nitrogen (BUN) and ‘serum creainine; monilasis, guia, presence of castsin urine, pos-renal acute renal failure, proteinuria, uretc obstruction, urlithiasis (nin renal cobe) and transient imparment of renal function (e.g, decreased GFR) combined with cholelithiasis and vagintisicandidal vaginitis Very rare cases of nephraithiasis (renal preciptation) have been reported, mostly in children »3.years old who have been treated with her high daily doses (e.9., 2 £0 mg/kg/day) or total doses exceeding 10 g and with other rick factors such as dehydration or immobiization. This event may be symptomatic or asymptomatic, maylead to renalimpirmert, and is reversible upon discontinuation of ceftriaxone, Hematologic: Hematologic effects. are among the most frequent AEs reported with ceftiaxone which include anemia (induding hemolytic anemia), coagulopathy, eosinophilia, granulacytopenia,isoited cases of agranulocytosis; norease or decrease in hematocrit leukopenia, lymphopenia, neutropenia, thrombocytopenia, and thrombocytosis, prolongation of prothrombin time (with or without bleeding), serumsickness, Fatal hematyti reactions have been reportedin atleast one adult and two children who received cefaxone. These reactions acourred shortly afer adminstration of a cefiaxone dose and consssted of severe intravascular hemolysis and anemia, decreased hemoglobin cconcenirations, reticulocytnsis, hemoglobinuria, and cardiac arrest. In atleast one case, the direct antilobulin (Coombs) test was ‘stongly postive andthe patients serum agglutinated washed erythrocytesin the presence of complement andoeftiaxone. Hepatobiliary: Increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT), alkaline phosphatase and bilirubin; biliary conditions (¢.q_, cholecystitis, cholelithiasis) occurred inpatients diagnosed with Lyme disease, Jaundice and kemicterus Reports (in asymptomatic and symplomatic patients) of utrasonographic shadows euagesting precipitation inthe gallbladder and of gallbladder sludge which have been accompanied by clinical symptoms such 2s pain, nauséa and vomiting (these abnormalities appear (on sonography as an echo without acoustical shadowing suggesting sludge or an echo with acoustical shadowing which may be misinterpreted as gallstones. The chemical nature ofthe sonogranhically detected material has been determined io be predominantly a cefirrane-calciumsatt) Other Adverse Effects: Anaphyiactic shock, antibiass resistance burning tongue, dlaphoresis (with diated pups) and fusing, gloticlaryngeal edema, malaise, oral candidias's andiwerigo Other rarely observed reactions include allergic pneumonitis, anaphylaxis, anaphylactoid reactions, basophilia, bronchospasm, coagulation disorders, decrease in prothrombin time, epistaxis, leukocytosis, Iymphocytosss, monocytosis, hypoprothrombinemia, palpitations, restlessness, serumsickness, seczures andshivering Inadetion to the adverse reactions sted above which have been observed in patents treated with ceffraxone, the folowing AES have beenreported or cephalosporin-class antibiotic: Allergic reactions, aplastic anemia, drug fever, hemorthage, hepatic dysfunction including cholestasis, hypertonia, nephropathy, renal dysfunction, serum sickness ike reaction, tonic, reversiblehyperacivityand superinfection. OVERDOSE AND TREATMENT There is no specific antidote. In case af overdosage, hemodialysis or peritoneal cialysis wil not reduce drug concentration, Treatment of overdosage should be symptomatic. ADVERSE DRUG REACTION REPORTING STATEMENT For suspected adverse drug reaction, seek medical attention immediately and regort fo the FDA at wwwida.goveh AND Unilab at (+632) 858-1000 or productsafety@@urdab.com ph. By reporting undesirable effects, you can help provide more infoematon on the: safety of this medicine. ‘STORAGE CONDITIONS + Store cefiraxane powder for injection at temperatures not exoeeding 30°C. * Protect from light + Keep the product aut of sight and reach of children Caution : Foods, Drugs, Devices, and Cosmetics Act prohibits dispensin without prescription AVAILABILITY Ceftriaxone Sodium (FORGRAN*) 600mg vial Powder for Injection with 5 mL. Ampule Sterile Water for Injection Ceftrawone Sodium (FORGRAM* 1 gram vial Powder for Injection with 10 mL. Ampule Sterle Water for Injection Manufactured by PT Darye-Varia Laboratoria Tok Rp J Lanbau Liobana (d ») RT.007 RW.008, Kel. + Karangasem BaratKec. Citeureup Trusted Quality Healthcare, Bogor Jawa Barat- Indonesia Imported and Distrbuted by UNILAB, Inc. ‘No. 66United Street , Mandaluyong City Metre Mania. Priippines Date of First Authorization: Forgram (Cefiriaxone as Sodium) 1g Powder for Injection - DR-XY35813 - 13 May 2008 Forgram (Ceftraxone 2s: Sodium) 500 mg Powder for Injection - DR-XY35512— 13 May 2003 iBIn41487IN03 Revision Date: January 2018 Reg IPOPHIL