AugTaz Injection 125mg / 250mg / 500mg / 1g

AugTaz-KID 125 mg

Each vial contains :

Ceftriaxone Sodium IP equivalent to Ceftriaxone 125 mg

Tazobactam Sodium IP equivalent to Tazobactam 15.625 mg

This pack contains Sterile Water for Injections IP 5 ml.

AugTaz-250 mg

Each vial contains :

Ceftriaxone Sodium IP equivalent to Ceftriaxone 250 mg

Tazobactam Sodium IP equivalent to Tazobactam 31.25 mg

This pack contains Sterile Water for Injections IP 5 ml.

AugTaz-500 mg

Each vial contains :

Ceftriaxone Sodium IP equivalent to Ceftriaxone 500 mg

Tazobactam Sodium IP equivalent to Tazobactam 62.5 mg

This pack contains Sterile Water for Injections IP 5 ml.

AugTaz-1 g

Each vial contains :

Ceftriaxone Sodium IP equivalent to Ceftriaxone 1.0 g

Tazobactam Sodium IP equivalent to Tazobactam 125 mg

This pack contains Sterile Water for Injections IP 10 ml.

AugTazis a combination of Ceftriaxone, a semi - synthetic third generation broad spectrum cephalosporin antibiotic along with a β- lactamase inhibitor Tazobactam. Tazobactam sodium, a derivative of the penicillin nucleus, is a penicillanic acid sulfone.

Ceftriaxone Sodium :

Chemical Name : (6R, 7R)-7-[2-(2-Amino-4-thiazolyl) glyoxylamido]-8-oxo-3- Chemical Name : (2S,3S,5R)-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl) [[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo -4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate-4,4-dioxide. [4.2.0]oct-2-ene-2-carboxylic acid, 72-(Z)-(O-methyloxime), disodium salt, sesquaterhydrate.

Molecular Formula :C₁₈H₁₆N₈Na₂O₇S₃•3.5H₂O

Molecular Weight : 661.59

RATIONALE OF THE COMBINATION :

Ceftriaxone is a third generation semi-synthetic parenteral cephalosporin that has excellent activity against variety of gram -ve organisms and some gram +ve organisms like Streptococcus pneumoniae, Staphylococcus aureus, H.influenzae, Neisseria meningitides and members of Enterobacteriaceae. Ceftriaxone is indicated in number of community and hospital acquired infections caused by the susceptible organisms both in adults and in children including neonates. Tazobactam is penicillanic acid sulfone derivative with beta-lactamase inhibitory properties, having good affinity for a variety of both plasmid mediated and chromosomal beta lactamases produced by gram +ve and gram –ve bacteria which are originally sensitive to Ceftriaxone. Therefore, it enhances the activity of penicillins and cephalosporins against many resistant strains of bacteria. It is regarded as more potent than other β-lactamase inhibitors (like sulbactam). Clinical role of Ceftriaxone can be compromised due to increasing proportion of extended spectrum β-lactamase (ESBL) producing bacteria which exhibit resistance to Ceftriaxone. To treat such infections Ceftriaxone can be combined with a beta lactamases inhibitor of better efficacy like Tazobactam. The combination of Ceftriaxone and Tazobactam will be effective not only against the beta lactamase producing organisms but also against the originally Ceftriaxone-susceptible bacteria.

Ceftriaxone is a third generation semi-synthetic parenteral cephalosporin that has excellent activity against variety of gram -ve organisms and some gram +ve organisms like Streptococcus pneumoniae, Staphylococcus aureus, H.influenzae, Neisseria meningitides and members of Enterobacteriaceae. Ceftriaxone is indicated in number of community and hospital acquired infections caused by the susceptible organisms both in adults and in children including neonates. Tazobactam is penicillanic acid sulfone derivative with beta-lactamase inhibitory properties, having good affinity for a variety of both plasmid mediated and chromosomal beta lactamases produced by gram +ve and gram –ve bacteria which are originally sensitive to Ceftriaxone. Therefore, it enhances the activity of penicillins and cephalosporins against many resistant strains of bacteria. It is regarded as more potent than other β-lactamase inhibitors (like sulbactam). Clinical role of Ceftriaxone can be compromised due to increasing proportion of extended spectrum β-lactamase (ESBL) producing bacteria which exhibit resistance to Ceftriaxone. To treat such infections Ceftriaxone can be combined with a beta lactamases inhibitor of better efficacy like Tazobactam. The combination of Ceftriaxone and Tazobactam will be effective not only against the beta lactamase producing organisms but also against the originally Ceftriaxone-susceptible bacteria.

Ceftriaxone is a parenteral cephalosporin which acts by inhibition of cell wall biosynthesis and thus is bactericidal in its action. It has excellent activity against variety of aerobic and anaerobic, gram-positive and gram-negative pathogens. Tazobactam (sodium) is a new β-lactamase inhibitor with a range of activity that includes extended spectrum plasmid mediated beta lactamases. Tazobactam lacks significant antibacterial activity of its own. It combines irreversibly with the common plasmid-encoded β-lactamases including the extended spectrum group of beta lactamases. By rendering β–lactamase inactive, Tazobactam is able to protect the activity of Ceftriaxone.

MICROBIOLOGY :

AugTaz has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections.

Aerobic gram-negative microorganisms

• Escherichia coli
• Haemophilus influenzae (including ampicillin-resistant and β-lactamase producing strains)
• Klebsiella pneumoniae
• Moraxella catarrhalis (including β--lactamase producing strains)
• Morganella morganii
• Neisseria gonorrhoeae (including penicillinase- and nonpenicillinase-producing strains)
• Neisseria meningitidis
• Proteus spp
• Serratia marcescens
• Ceftriaxone is also active against many strains of Pseudomonas aeruginosa

Aerobic gram-positive microorganisms

• Staphylococcus aureus (including penicillinase-producing strains)
• Staphylococcus epidermidis
• Streptococcus pneumoniae
• Streptococcus pyogenes
• Viridans group streptococci

Anaerobic microorganisms

• Bacteroides fragilis
• Clostridium species
• Peptostreptococcus species

Absorption

Ceftriaxone demonstrates nonlinear dose-dependent pharmacokinetics because of its protein binding. Mean peak plasma concentrations of about 40 and 80 micrograms/mL have been reported 2 hours after intramuscular injection of 0.5 and 1 g of Ceftriaxone respectively. Mean peak plasma concentrations after bolus intravenous injection are about 120 mg/l following a 500 mg dose and about 200 mg/l following a 1g dose.

Distribution

Ceftriaxone is widely distributed in body tissues and fluids. It crosses both inflamed and non-inflamed meninges, generally achieving therapeutic concentrations in the CSF. Tazobactam is widely distributed into tissues and body fluids including, intestinal mucosa, gallbladder, lung, female reproductive tissues (uterus, ovary and fallopian tube) interstitial fluid and bile. The protein binding of Ceftriaxone is 85-95% and that of Tazobactam is 30%.

Metabolism & Excretion

About 40-65% of a dose of Ceftriaxone is excreted unchanged in urine. The remainder is excreted in bile. The plasma half life of Ceftriaxone is not dose-dependent and varies between 6-9 hours. Tazobactam and its metabolite is eliminated primarily by renal excretion with 80% of the administered dose excreted as unchanged drug and the remainder as the single metabolite.

AugTaz is indicated for the treatment of the following infections when caused by susceptible organisms :

• Respiratory Tract Infections and Pneumonia
• Bacterial Septicemia
• Uncomplicated Gonorrhea (Cervical/Urethral and rectal)
• Surgical Prophylaxis
• Intra-Abdominal Infections
• Urinary Tract Infections (Complicated and Uncomplicated)
• Bone and Joint Infections
• Skin and Skin Structure Infections
• Acute bacterial otitis media
• Meningitis
• Pelvic Inflammatory Disease

Adults

The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. For infections caused by Staphylococcus aureus (MSSA), the recommended daily dose is 2 to 4 grams, in order to achieve >90% target attainment. The total daily dose should not exceed 4 grams. If Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism. For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended. Generally, Ceftriaxone Injection therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required. When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.No dosage adjustment is necessary for patients with impairment of renal or hepatic function.

Pediatric Patients

For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams. For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams. In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.

Neonates

Hyperbilirubinemic neonates, especially prematures, should not be treated with Ceftriaxone Injection. The product may be administered by deep intramuscular injection or as a slow intravenous injection after reconstitution of the solution according to the directions given below. The dosage and mode of administration should be determined by the severity of the infection, susceptibility of the causative organism and the patient’s condition.

Intramuscular injection :Contents of one vial should be dissolved in 0.45 ml of Sterile Water for Injections IP for AugTaz-KID 125 mg of injection, 0.9 ml of Sterile Water for Injections IP for AugTaz-250 mg injection, 1.8 ml of Sterile Water for Injections IP for AugTaz-500 mg injection and 3.6 ml of Sterile Water for Injections IP for AugTaz-1 g injection. The solution should be administered by deep intramuscular injection. Doses greater than 1 g (of Ceftriaxaone) should be divided and injected at more than one site.

Intravenous injection : Contents of one vial should be dissolved in 1.2 ml of Sterile Water for Injections IP for AugTaz-KID 125 mg of injection, 2.4 ml of Sterile Water for Injections IP for AugTaz-250 mg injection, 4.8 ml of Sterile Water for Injections IP for AugTaz-500 mg injection and 9.6 ml of Sterile Water for Injections IP for AugTaz-1 g injection. The solution should be administered over at least 2-4 minutes, directly into the vein or via the tubing of an intravenous infusion

AugTaz should not be given to patients with a history of hypersensitivity to Cephalosporins, Penicillins or β-lactamase inhibitors

For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams. For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams. In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.

Pregnancy : Pregnancy Category B.

There are no adequate and well-controlled studies in pregnant women and AugTaz should be used during pregnancy only if clearly needed.

Nursing Mothers :

Low concentrations of Ceftriaxone are excreted in human milk. Caution should be exercised when Ceftriaxone for injection is administered to a nursing woman

Pediatric Use :

Safety and effectiveness of Ceftriaxone for injection in neonates, infants and pediatric patients have been established. In vitro studies have shown that Ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin.

Clostridium difficile :

Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including Ceftriaxone, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Interaction with Calcium - Containing products

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of Ceftriaxone-calcium can also occur when Ceftriaxone is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, Ceftriaxone and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid. In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of Ceftriaxone-calcium.

Probenecid : The elimination of Ceftriaxone is not altered by probenecid.

Aminoglycoside antibiotics and diuretics: No impairment of renal function has so far been observed after concurrent administration of large doses of Ceftriaxone and potent diuretics (e.g.furosemide). There is no evidence that Ceftriaxone increases renal toxicity of aminoglycosides.

Alcohol : No effect similar to that of disulfiram has been demonstrated after ingestion of alcohol subsequent to the administration of Ceftriaxone

Antibiotics : In an in vitro study, antagonistic effects have been observed with the combination of chloramphenicol and Ceftriaxone

Anticoagulants : As Ceftriaxone has an N-methylthiotriazine side-chain, it might have the potential to cause hypoprothrombinaemia resulting in an increased risk of bleeding in patients treated with anticoagulants

Oral Contraceptives : Ceftriaxone may adversely affect the efficacy of oral hormonal contraceptives. Consequently, it is advisable to use supplementary (non-hormonal) contraceptive measures during treatment and in the month following treatment. Based on literature reports Ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole and aminoglycosides.

Interference with Laboratory Tests

In patients treated with Ceftriaxone, the Coombs' test may in rare cases be false-positive

Ceftriaxone for injection is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to ceftriaxone for injection therapy or of uncertain etiology, were observed :

Local reactions : Pain, induration, tenderness, phlebitis; General disorders and administration site conditions : Injection site pain; Hypersensitivity : Rash. Less frequently reported were pruritus, fever or chills; Infections and Infestations : Genital fungal infection Hematologic : Eosinophilia, thrombocytosis and leukopenia. Less frequently reported were anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia and prolongation of the prothrombin time; Blood and Lymphatic disorders : Granulocytopenia, coagulopathy; Gastrointestinal : Diarrhea/loose stools. Less frequently reported were nausea or vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment; Hepatic : Elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Less frequently reported were elevations of alkaline phosphatase and bilirubin; Renal : Elevations of the BUN. Less frequently reported were elevations of creatinine and the presence of casts in the urine. Central Nervous System : Headache or dizziness were reported occasionally; Genitourinary : Moniliasis or vaginitis were reported occasionally. Skin and mucous membranes : Stevens-Johnson syndrome (SJS) is reported. Miscellaneous : Diaphoresis and flushing were reported occasionally. Other rarely observed adverse reactions include abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, seizures, and serum sickness. Investigations : Blood creatinine increased.

Cephalosporin class adverse reactions

In addition to the adverse reactions listed above which have been observed in patients treated with ceftriaxone, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibiotics :

Adverse reactions

Allergic reactions, drug fever, serum sickness-like reaction, renal dysfunction, toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, and superinfection.

Altered laboratory tests

Positive direct Coombs' test, false-positive test for urinary glucose, and elevated LDH. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

In the case of overdose nausea, vomiting and diarrhoea can occur. Ceftriaxone concentration can not be reduced by haemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is symptomatic.

Store below 30°C. Protect from light & moisture

Keep out of reach of children. After reconstitution, do not use in case any foreign particulate matter is observed inside the vial.

Refer on the pack.

AugTaz-KID 125 mg : A vial of 140.625 mg with SWFI IP 5 ml.

AugTaz-250 mg : A vial of 281.25 mg with SWFI IP 5 ml.

AugTaz-500 mg : A vial of 562.5 mg with SWFI IP 5 ml.

AugTaz-1 g : A vial of 1.125 g with SWFI IP 10 ml.