Tefno™
[Ceftriaxone]
Indications
Severe respiratory and genitor UTI's, bone and joint infections, abdominal infections, sepsis & meningitis.
Contraindication
Tefno is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.
Neonates (< 28 days)
Hyperbilirubinemic neonates, especially prematures, should not be treated with Tefno. In vitro studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin and bilirubin encephalopathy can possibly develop in these patients.
Tefno is contraindicated in neonates if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium.
A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving Tefno and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Tefno and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom Tefno and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates.
Drug Interactions
Interactions between ceftriaxone and other drugs have not been fully evaluated.
Side Effects
Tefno is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to Tefno therapy or of uncertain etiology, were observed:
LOCAL REACTIONS - pain, induration and tenderness was 1% overall. Phlebitis was reported in < 1% after IV administration. The incidence of warmth, tightness or induration was 17% (3/17) after IM administration of 350 mg/mL and 5% (1/20) after IM administration of 250 mg/mL.
HYPERSENSITIVITY - rash (1.7%). Less frequently reported (< 1%) were pruritus, fever or chills.
HEMATOLOGIC - eosinophilia (6%), thrombocytosis (5.1%) and leukopenia (2.1%). Less frequently reported (< 1%) were anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia and prolongation of the prothrombin time.
GASTROINTESTINAL - diarrhea (2.7%). Less frequently reported (< 1%) were nausea or vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (see WARNINGS).
HEPATIC - elevations of SGOT (3.1%) or SGPT (3.3%). Less frequently reported (< 1%) were elevations of alkaline phosphatase and bilirubin.
RENAL - elevations of the BUN (1.2%). Less frequently reported (< 1%) were elevations of creatinine and the presence of casts in the urine.
CENTRAL NERVOUS SYSTEM - headache or dizziness were reported occasionally (< 1%).
GENITOURINARY - moniliasis or vaginitis were reported occasionally (< 1%).
MISCELLANEOUS - diaphoresis and flushing were reported occasionally (< 1%).
Other rarely observed adverse reactions (< 0.1%) 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.
Warning and Precautions
Hypersensitivity
BEFORE THERAPY WITH TEFNO IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS, PENICILLINS OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE THE USE OF SUBCUTANEOUS EPINEPHRINE AND OTHER EMERGENCY MEASURES.
Interaction with Calcium-Containing Products
Do not use diluents containing calcium, such as Ringer's solution or Hartmann's solution, to reconstitute Tefno vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone calcium can also occur when Tefno is mixed with calcium-containing solutions in the same IV administration line. Tefno 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, Tefno 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.
Clostridium difficile
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Tefno, 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.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
General
Prescribing Tefno in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Although transient elevations of BUN and serum creatinine have been observed, at the recommended dosages, the nephrotoxic potential of Tefno is similar to that of other cephalosporins.
Ceftriaxone is excreted via both biliary and renal excretion. Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of Tefno are administered.
Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the Tefno dosage should not exceed 2 gm daily.
Alterations in prothrombin times have occurred rarely in patients treated with Tefno. Patients with impaired vitamin K synthesis or low vitamin K stores (eg, chronic hepatic disease and malnutrition) may require monitoring of prothrombin time during Tefno treatment. Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy.
Prolonged use of Tefno may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Tefno should be prescribed with caution in individuals with a history of gastrointestinal disease, especially colitis.
There have been reports of sonographic abnormalities in the gallbladder of patients treated with Tefno; some of these patients also had symptoms of gallbladder disease. These abnormalities appear on sonography as an echo without acoustical shadowing suggesting sludge or as an echo with acoustical shadowing which may be misinterpreted as gallstones. The chemical nature of the sonographically detected material has been determined to be predominantly a ceftriaxone-calcium salt. The condition appears to be transient and reversible upon discontinuation of Tefno and institution of conservative management.Therefore, Tefno should be discontinued in patients who develop signs and symptoms suggestive of gallbladder disease and/or the sonographic findings described above.
Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported rarely in patients treated with Tefno. Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of Tefno-related biliary precipitation cannot be ruled out.
As with other cephalosporins, anaphylactic shock cannot be ruled out even if a thorough patient history is taken.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: Considering the maximum duration of treatment and the class of the compound, carcinogenicity studies with ceftriaxone in animals have not been performed. The maximum duration of animal toxicity studies was 6 months.
Mutagenesis
Genetic toxicology tests included the Ames test, a micronucleus test and a test for chromosomal aberrations in human lymphocytes cultured in vitro with ceftriaxone. Ceftriaxone showed no potential for mutagenic activity in these studies.
Impairment of Fertility
Ceftriaxone produced no impairment of fertility when given intravenously to rats at daily doses up to 586 mg/kg/day, approximately 20 times the recommended clinical dose of 2 gm/day.
Pregnancy
Teratogenic Effects
Pregnancy Category B. Reproductive studies have been performed in mice and rats at doses up to 20 times the usual human dose and have no evidence of embryotoxicity, fetotoxicity or teratogenicity. In primates, no embryotoxicity or teratogenicity was demonstrated at a dose approximately 3 times the human dose.
There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nonteratogenic Effects
In rats, in the Segment I (fertility and general reproduction) and Segment III (perinatal and postnatal) studies with intravenously administered ceftriaxone, no adverse effects were noted on various reproductive parameters during gestation and lactation, including postnatal growth, functional behavior and reproductive ability of the offspring, at doses of 586 mg/kg/day or less.
Nursing Mothers
Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when Tefno is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of Tefno in neonates, infants and pediatric patients have been established for the dosages described in the DOSAGE section. In vitro studies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin. Tefno should not be administered to hyperbilirubinemic neonates, especially prematures.
Geriatric Use
Of the total number of subjects in clinical studies of Tefno, 32% were 60 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
The pharmacokinetics of ceftriaxone were only minimally altered in geriatric patients compared to healthy adult subjects and dosage adjustments are not necessary for geriatric patients with ceftriaxone dosages up to 2 grams per day.
Dosage
Tefno may be administered intravenously or intramuscularly.
NEONATES: Hyperbilirubinemic neonates, especially prematures, should not be treated with Tefno.
Tefno is contraindicated in neonates if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxonecalcium .
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 acute bacterial otitis media, a single intramuscular dose of 50 mg/kg (not to exceed 1 gram) is recommended.
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.
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. 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 the treatment of uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended.
For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended.
Generally, Tefno 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.
Presentations Available
Tefno is supplied as a sterile crystalline powder in glass vials. The following packages are available:
Vials containing 250 mg equivalent of ceftriaxone with/without Lignocain.
Vials containing 500 mg equivalent of ceftriaxone. with/without Lignocain
Vials containing 1 gm equivalent of ceftriaxone. with/without Lignocain
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