# Brand Name Generic & Strenght Dosage Form Pack Size
1 Oryx 250 IV Ceftriaxone Sodium 250 mg IV Injection 1 X 1's
2 Oryx 500IV Ceftriaxone Sodium 500mg IV Injection 1 X 1's
3 Oryx 1g IV Ceftriaxone Sodium 1g IV Injection 1 X 1's
4 Oryx 1g IV 5's Ceftriaxone Sodium 1g IV Injection 5 X 1's
5 Oryx 2gIV Ceftriaxone Sodium 2g IV Injection 1 X 1's
6 Oryx 250 Im Ceftriaxone Sodium 250mg IM Injection 1 X 1's
7 Oryx 500 IM Ceftriaxone Sodium 500mg IM Injection 1 X 1's
8 Oryx 1g IM Ceftriaxone Sodium 1g IM Injection 1 X 1's

Oryx®

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Oryx® (Ceftriaxone Sodium) injection and other antibacterial drugs, Oryx® injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Description

Oryx® is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous or intramuscular administration. Ceftriaxone Sodium is (6R,7R)-7-[2-(2-Amino-4-thiazolyl) glyoxylamido]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylicacid, 72 -(Z)-(O-methyloxime), disodium salt, sesquaterhydrate. The empirical formula of Ceftriaxone Sodium is C18H16N8Na2O7S3. 3.5 H2O. It has a calculated molecular weight of 661.59 and the following structural formula

Oryx® is a white to yellowish-orange crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 1% aqueous solution is approximately 6.7. The color of Oryx® solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used. Oryx® contains approximately 83 mg (3.6 mEq) of sodium per gram of Ceftriaxone activity.

Composition

Oryx® 250 mg IM/IV Injection: Each vial contains dry substance equivalent to 250 mg Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by a solvent ampoule of 2 ml Lidocaine HCI USP 1% Injection for IM injection or 5 ml Water for Injection USP for IV injection.

Oryx® 500 mg IM/IV Injection: Each vial contains dry substance equivalent to 500 mg Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by a solvent ampoule of 2 ml Lidocaine HCI USP 1% Injection for IM injection or 5 ml Water for Injection USP for IV injection.

Oryx® 1 g IM/IV Injection: Each vial contains dry substance equivalent to 1 g Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by a solvent ampoule of 3.5 ml Lidocaine HCI USP 1% Injection for IM injection or 10 ml Water for Injection USP for IV injection.

Oryx® 2 g IV Injection: Each vial contains dry substance equivalent to 2 g Ceftriaxone (as sterile Ceftriaxone Sodium USP) and each of two ampoules contains 10 ml Water for Injection USP for IV injection.

Microbiology

The bactericidal activity of Ceftriaxone results from inhibition of cell wall synthesis. Ceftriaxone has a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria. Ceftriaxone is usually active against most strains of the following microorganisms, both in vitro and in clinical infections. Aerobic gram - negative microorganisms: Acinetobacter calcoaceticus, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including ampicillin-resistant and beta-lactamase producing strains), Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (including beta-lactamase producing strains), Morganella morganii, Neisseria gonorrhoeae (including penicillinase- and nonpenicillinase - producing strains), Neisseria meningitides, Proteus mirabilis, Proteus vulgaris, Serratia marcescens. Ceftriaxone is also active against many strains of Pseudomonas aeruginosa. Note: Many strains of the above organisms that are multiply resistant to other antibiotics, e.g., penicillins, cephalosporins, and aminoglycosides are susceptible to Ceftriaxone. Aerobic gram - positive microorganisms: Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Viridans group streptococci. Note: Methicillin-resistant staphylococci are resistant to cephalosporins, including Ceftriaxone. Most strains of Group D streptococci and enterococci, eg. Enterococcus (Streptococcus) faecalis are resistant. Anaerobic microorganisms: Bacteroides fragilis, Clostridium species, Peptostreptococcus species. Note: Most strains of Clostridium difficile are resistant.

Pharmacokinetic

The pharmacokinetics of Ceftriaxone are nonlinear and all basic pharmacokinetic parameters, except the elimination half life, are dose dependent if based on total drug concentrations. Absorption: The maximum plasma concentration after a single IM dose of 1 g is about 81 mg/L and is reached in 2-3 hours after administration. The area under the plasma concentration-time curve after IM administration is equivalent to that after IV administration of an equivalent dose, indicating 100% bioavailability of intramuscularly administered Ceftriaxone. Distribution: The volume of distribution of Ceftriaxone is 7-12 L. Ceftriaxone has shown excellent tissue and body fluid penetration after a dose of 1-2 g; concentrations well above the minimal inhibitory concentrations of most pathogens responsible for infections are detectable for more than 24 hours in over 60 tissues or body fluids including lung, heart, biliary tract/liver, tonsil, middle ear and nasal mucosa, bone as well as cerebrospinal, pleural, prostatic and synovial fluids. On intravenous administration, Ceftriaxone diffuses rapidly into the interstitial fluid, where bactericidal concentrations against susceptible organisms are maintained for 24 hours. Protein binding: Ceftriaxone is reversibly bound to albumin, and the binding decreases with the increase in concentration, e.g. from 95% binding at plasma concentrations of < 100 mg/L to 85% binding at 300 mg/L. Owing to the lower albumin content, the proportion of free Ceftriaxone in interstitial fluid is correspondingly higher than in plasma. Metabolism: Ceftriaxone is not metabolized systemically; but is converted to inactive metabolites by the gut flora. Elimination: Total plasma clearance is 10-22 ml/min. Renal clearance is 5-12 ml/min. 50-60% of Ceftriaxone is excreted unchanged in the urine, while 40-50% is excreted unchanged in the bile. The elimination half-life in adults is about 8 hours.

Indication and Use

Oryx® is indicated for the treatment of the following infections when caused by susceptible organisms: Lower respiratory tract infections, Acute bacterial otitis media, Skin and skin-structure infections, Urinary tract infections (complicated and uncomplicated), Uncomplicated gonorrhea (cervical/urethral and rectal), Pelvic inflammatory disease, Bacterial septicemia, Bone and joint infections, Intra-abdominal infections, Meningitis and in Surgical prophylaxis.

Dosage and Administration

Oryx® can be administered either intravenously or intramuscularly. Dosage and mode of administration should be determined by severity of infection, susceptibility of causative organisms and the patient's condition. Under most circumstances, once-daily dose or in the specified indications, a single dose will give satisfactory therapeutic results. Adults and children over 12 years: The usual dosage is 1-2 g of Oryx® once daily (every 24 hours). In severe cases or in infections caused by moderately sensitive organisms, the dosage may be raised to 4 g once daily. Neonates, infants and children up to 12 years: The following dosage schedules are recommended for once daily administration. Neonates (up to 14 days): A daily dose of 20-50 mg/kg bodyweight, not to exceed 50 mg/kg, on account of the immaturity of the infant's enzyme systems. It is not necessary to differentiate between premature and term infants. Infants and children (15 days to 12 years): A daily dose of 20-80 mg/kg. For children with bodyweights of 50 kg or more, the usual adult dosage should be used. Intravenous doses of > 50 mg/kg body weight should be given by infusion over at least 30 minutes. Elderly patients: The dosages recommended for adults require no modification in case of geriatric patients. Duration of therapy: Oryx® 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. Combination therapy: Synergy between Ceftriaxone and aminoglycosides has been demonstrated with many gram-negative bacilli under experimental conditions. Although enhanced activity of such combinations is not always predictable, it should be considered in severe and 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. Meningitis: In bacterial meningitis in infants and children, treatment begins with doses of 100 mg/kg (not to exceed 4 g) once daily. As soon as the causative organism has been identified and its sensitivity determined, the dosage can be reduced accordingly. Best results have been found with the following duration of therapy: Neisseria meningitidis-4 days, Haemophilus influenzae-6 days, Streptococcus pneumoniae-7 days, Susceptible Enterobacteriaceae-10 to 14 days. Gonorrhoea (penicillinase - producing and nonpenicillinase - producing strains): a single IM dose of 250 mg Oryx® is recommended. Perioperative prophylaxis: A single dose of 1-2 g depending on the risk of infection of 30-90 minutes prior to surgery. In colorectal surgery, administration of Oryx® with or without a 5-nitroimidazole, e.g. Ornidazole, has been proven effective. Impaired renal and hepatic function: In patients with impaired renal function, there is no need to reduce the dosage of Oryx® provided hepatic function is intact. Only in cases of preterminal renal failure (creatinine clearance <10 ml/min) should the Oryx® dosage not exceed 2 g daily. In patients with liver damage, there is no need for the dosage to be reduced provided renal function is intact. In patients with both severe renal and hepatic dysfunction, the plasma concentrations of Ceftriaxone should be determined at regular intervals and, if necessary, the dose should be adjusted. In patients undergoing dialysis, no additional supplementary dosing is required following the dialysis. Plasma concentrations should, however, be monitored, to determine whether dosage adjustments are necessary, since the elimination rate in these patients may be altered.

Directions for use

Intramuscular Injection: For IM injection, Oryx® 250 mg or Oryx® 500 mg is dissolved in 2 ml and Oryx® 1 g in 3.5 ml of Lidocaine HCl 1% solution and administered by deep intragluteal injection. It is recommended that not more than 1 g be injected at one site. The Lidocaine solution must never be administered intravenously. Intravenous Injection: For IV injection, Oryx® 250 mg or Oryx® 500 mg is dissolved in 5 ml, Oryx® 1 g in 10 ml and Oryx® 2 g in 20 ml of Water for Injection. The injection should be administered over 2-4 minutes, directly into the vein or via the tubing of an intravenous infusion.

Contraindication

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

Use in Pregnancy and Lactation

Pregnancy: The safety of Ceftriaxone in the treatment of infections during pregnancy has not been established. Ceftriaxone should only be used during pregnancy if the likely benefit outweighs the potential risk to the fetus and/or the mother. Lactation: Ceftriaxone is excreted in breast milk at low concentrations. Therefore, caution should be exercised when Ceftriaxone is administered to a nursing mother.

Side Effect

Ceftriaxone is generally well-tolerated. During the treatment, the following side effects, which were reversible either spontaneously or after withdrawal of the drug, have been observed : Systemic side effects- Gastrointestinal complaints (about 2% of cases): loose stools or diarrhoea, nausea, vomiting, stomatitis and glossitis. Hematological changes (about 2%): eosinophilia, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia. Skin reactions (about 1%): exanthema, allergic dermatitis, pruritus, urticaria, edema, erythema multiforme. Other, rare side effects: headache and dizziness, increase in liver enzymes, gallbladder sludge, oliguria, increase in serum creatinine, mycosis of the genital tract, shivering and anaphylactic or anaphylactoid reactions. Pseudomembranous enterocolitis and coagulation disorders have been reported as very rare side effects. Local side effects- In rare cases, phlebitic reactions occurred after IV administration. These may be minimized by slow (two to four minutes) injection. Intramuscular injection without Lidocaine solution is painful.

Precaution

Ceftriaxone is excreted via both biliary and renal route. Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of Ceftriaxone is administered but concentrations of drug in the serum should be monitored periodically. If evidence of accumulation exists, dosage should be decreased accordingly. Although transient elevations in BUN (Blood Urea Nitrogen) and serum creatinine have been observed at recommended dosage nephrotoxic potential of Ceftriaxone is similar to that of other cephalosporins. Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, Ceftriaxone dosage should not exceed 2 gm daily without close monitoring of serum concentrations. Alternations in prothrombin times have occurred rarely in patients treated with Ceftriaxone. Patients with impaired vitamin-K synthesis or low vitamin-K stores (e.g. chronic hepatic disease and malnutrition) may require monitoring of prothrombin time during Ceftriaxone treatment. Vitamin-K (administration 10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy. Prolonged use of Ceftriaxone may result in overgrowth of non-susceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken. Ceftriaxone should be prescribed with caution in individuals with a history of gastrointestinal disease, especially colitis.

Warning

Before therapy with Ceftriaxone is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins and other drugs. This product should be given cautiously to penicillin hypersensitive patients. Serious acute hypersensitivity reactions may require the use of subcutaneous epinephrine and other emergency measures. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including Ceftriaxone and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who develop diarrhoea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of Clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of antibiotic-associated colitis.

Drug Interaction

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. No effect similar to that of Disulfiram has been demonstrated after ingestion of alcohol subsequent to the administration of Ceftriaxone. Ceftriaxone does not contain N-methylthiotetrazole moiety associated with possible ethanol intolerance and bleeding problems of certain other cephalosporins. The elimination of Ceftriaxone is not altered by Probenecid.

Stability and Storage Recommendation

Ceftriaxone sterile powder should be stored at room temperature (25°C to 30°C) or below and protected from light. After reconstitution, protection from normal light is not necessary. The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used. Reconstituted solutions retain their physical and chemical stability for 6 hours at room temperature and for 24 hours at 5°C. As a general rule, however the solutions should be used immediately after preparation.

Packaging Quantity

Oryx® Injection is supplied as a sterile crystalline powder in glass vials.

Oryx®  250 mg IV Injection : Pack of 1 vial containing 250 mg Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by one ampoule of 5 ml Water for Injection USP for IV injection, a sterile disposable syringe (5 ml) with a baby needle, a butterfly needle, an alcohol prep pad and a strip bandage.

Oryx®  250 mg IM Injection : Pack of 1 vial containing 250 mg Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by one ampoule of 2 ml Lidocaine HCI USP 1% Injection for IM injection, a sterile disposable syringe (5 ml) with a baby needle, an alcohol prep pad and a strip bandage.

Oryx®  500 mg IV Injection : Pack of 1 vial containing 500 mg Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by one ampoule of 5 ml Water for Injection USP for IV injection, a sterile disposable syringe (5 ml) with a baby needle, a butterfly needle, an alcohol prep pad and a strip bandage.

Oryx®  500 mg IM Injection : Pack of 1 vial containing 500 mg Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by one ampoule of 2 ml Lidocaine HCI USP 1% Injection for IM injection, a sterile disposable syringe (5 ml) with a baby needle, an alcohol prep pad and a strip bandage.

Oryx®  1 g IV Injection (Single pack) : Pack of 1 vial containing 1 g Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by one ampoule of 10 ml Water for Injection USP for IV injection, a sterile disposable syringe (10 ml) with an extra needle, a butterfly needle, an alcohol prep pad and a strip bandage.

Oryx®  1 g IV Injection (Five packs): Each box contains 5 blister packs. Each blister pack contains 1 vial containing 1 g Ceftriaxone (as sterile Ceftriaxone Sodium USP) and one ampoule of 10 ml Water for Injection USP for IV injection.

Oryx®  1 g IM Injection : Pack of 1 vial containing 1 g Ceftriaxone (as sterile Ceftriaxone Sodium USP) accompanied by one ampoule of 3.5 ml Lidocaine HCI USP 1% Injection for IM injection, a sterile disposable syringe (5 ml), an alcohol prep pad and a strip bandage.

Oryx®  2 g IV Injection : Pack of 1 vial containing 2 g Ceftriaxone (as sterile Ceftriaxone Sodium USP) and each of two ampoules contains 10 ml Water for Injection USP for IV injection, a sterile disposable syringe (20 ml), a butterfly needle, an alcohol prep pad and a strip bandage.