Ceftriaxone Sodium 500 mg Injection, Powder, For Solution, 1 vial — NDC 82804-066-01 (Billing 82804-0066-01)

WARNINGS Hypersensitivity Reactions Before therapy with Ceftriaxone for injection is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins and other beta-lactam agents or other drugs. This product should be given cautiously to penicillin and other beta-lactam agent-sensitive patients. Antibacterial drugs 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. As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions (i.e., anaphylaxis) have been reported. In case of severe hypersensitivity reactions, treatment with ceftriaxone must be discontinued immediately and adequate emergency measures must be initiated.

Interaction with Calcium-Containing Products Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone for injection 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 for injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for injection 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 for injection 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 (see CLINICAL PHARMACOLOGY , CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION ). Neurological Adverse Reactions Serious neurological adverse reactions have been reported during postmarketing surveillance with ceftriaxone use.

These reactions include encephalopathy (disturbance of consciousness including somnolence, lethargy, and confusion), seizures, myoclonus, and non-convulsive status epilepticus (see ADVERSE REACTIONS ). Some cases occurred in patients with severe renal impairment who did not receive appropriate dosage adjustment. However, in other cases, neurological adverse reactions occurred in patients receiving an appropriate dosage adjustment.

The neurological adverse reactions were reversible and resolved after discontinuation. If neurological adverse reactions associated with Ceftriaxone for Injection therapy occur, discontinue Ceftriaxone for Injection and institute appropriate supportive measures. Make appropriate dosage adjustments in patients with severe renal impairment (see DOSAGE AND ADMINISTRATION ).

Clostridiumdifficile -Associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Ceftriaxone for injection, 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. Appropr… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS 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 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. GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS— injection site pain (0.6%). HYPERSENSITIVITY —rash (1.7%).

Less frequently reported (<1%) were pruritus, fever or chills. INFECTIONS AND INFESTATIONS —genital fungal infection (0.1%). 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. BLOOD AND LYMPHATIC DISORDERS— granulocytopenia (0.9%), coagulopathy (0.4%). GASTROINTESTINAL —diarrhea/loose stools (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 aspartate aminotransferase (AST) (3.1%) or alanine aminotransferase (ALT) (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%).

INVESTIGATIONS —blood creatinine increased (0.6%). 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. Postmarketing Experience: In addition to the adverse reactions reported during clinical trials, the following adverse experiences have been reported during clinical practice in patients treated with Ceftriaxone for injection.

Data are generally insufficient to allow an estimate of incidence or to establish causation. 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 Ceftriaxone for injection and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Ceftriaxone for injection 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 Ceftriaxone for injection 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. GASTROINTESTINAL – pancreatitis, stomatitis and glossitis.

GENITOURINARY – oliguria, ureteric obstruction, post-renal acute renal failure. DERMATOLOGIC – exanthema, allergic dermatitis, urticaria, edema; acute generalized exanthematous pustulosis (AGEP) and isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell’s syndrome/toxic epidermal necrolysis) have been reported. HEMATOLOGICAL CHANGES: Isolated cases of agranulocytosis (< 500/mm 3 ) have been reported, most of them after 10 days of treatment and following total doses of 20 g or more.

NEUROLOGIC… [Excerpted — this section continues on DailyMed.]

PRECAUTIONS Development of Drug-resistant Bacteria Prescribing Ceftriaxone for injection 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. Prolonged use of Ceftriaxone for injection may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential.

If superinfection occurs during therapy, appropriate measures should be taken. Patients with Renal or Hepatic Impairment Ceftriaxone is excreted via both biliary and renal excretion (see CLINICAL PHARMACOLOGY ). Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of Ceftriaxone for injection 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 Ceftriaxone for injection dosage should not exceed 2 g daily. Ceftriaxone is not removed by peritoneal- or hemodialysis. In patients undergoing dialysis no additional supplementary dosing is required following the dialysis.

In patients with both severe renal and hepatic dysfunction, close clinical monitoring for safety and efficacy is advised. Effect on Prothrombin Time Alterations in prothrombin times have occurred in patients treated with Ceftriaxone for injection. Monitor prothrombin time during Ceftriaxone for injection treatment in patients with impaired vitamin K synthesis or low vitamin K stores (eg, chronic hepatic disease and malnutrition).

Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy. Concomitant use of ceftriaxone with Vitamin K antagonists may increase the risk of bleeding. Coagulation parameters should be monitored frequently, and the dose of the anticoagulant adjusted accordingly, both during and after treatment with ceftriaxone (see ADVERSE REACTIONS ).

Gallbladder Pseudolithiasis Ceftriaxone-calcium precipitates in the gallbladder have been observed in patients receiving Ceftriaxone for injection. These precipitates 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 probability of such precipitates appears to be greatest in pediatric patients.

Patients may be asymptomatic or may develop symptoms of gallbladder disease. The condition appears to be reversible upon discontinuation of ceftriaxone sodium and institution of conservative management. Discontinue ceftriaxone sodium in patients who develop signs and symptoms suggestive of gallbladder disease and/or the sonographic findings described above.

Urolithiasisand Post-Renal Acute Renal Failure Ceftriaxone-calcium precipitates in the urinary tract have been observed in patients receiving Ceftriaxone for injection and may be detected as sonographic abnormalities. The probability of such precipitates appears to be greatest in pediatric patients. Patients may be asymptomatic or may develop symptoms of urolithiasis, and ureteral obstruction and post-renal acute renal failure.

The condition appears to be reversible upon discontinuation of ceftriaxone sodium and institution of appropriate management. Ensure adequate hydration in patients receiving Ceftriaxone for injection. Discontinue Ceftriaxone for injection in patients who develop signs and symptoms suggestive of urolithiasis, oliguria or renal failure and/or the sonographic findings described above.

Pancreatitis Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported in patients treated with Ceftriaxone for injection. Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of Ceftriaxone for injection-relat… [Excerpted — this section continues on DailyMed.]