Ceftriaxone 2 g/50mL Injection, Solution — NDC 0338-5003-41 (Billing 00338-5003-41)

WARNINGS Hypersensitivity BEFORE THERAPY WITH CEFTRIAXONE INJECTION 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. As with other cephalosporins, anaphylactic reactions with fatal outcome have been reported, even if a patient is not known to be allergic or previously exposed. Interaction with Calcium-Containing Products Do not further dilute ceftriaxone injection with products containing calcium, such as Ringer’s solution or Hartmann’s solution, 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 (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 Injection therapy occur, discontinue Ceftriaxone Injection and institute appropriate supportive measures. Make appropriate dosage adjustments in patients with severe renal impairment (see DOSAGE AND ADMINISTRATION ). Clostridioides difficile Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Ceftriaxone 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.

Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. Hemolytic Anemia An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials including ceftriaxone. Severe cases of hemolytic anemia, inc… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS Ceftriaxone is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to ceftriaxone therapy or of uncertain etiology, were observed: LOCAL REACTIONS — pain, induration and tenderness was 1% overall. Phlebitis was reported in <1% after IV administration.

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.

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. 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 and calcium-containing fluids.

In some of these cases, the same intravenous infusion line was used for both ceftriaxone 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 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.

IMMUNE SYSTEM DISORDER – Acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction. GASTROINTESTINAL – stomatitis and glossitis. GENITOURINARY – oliguria.

DERMATOLOGIC – exanthema, allergic dermatitis, urticaria, edema. As with many medications, isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell’s syndrome/toxic epidermal necrolysis) have been reported. NEUROLOGIC – Encephalopathy, seizures, myoclonus, and non-convulsive status epilepticus (see WARNINGS AND PRECAUTIONS ).

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, fall in prothrombin activity, and superinfection.

Altered Laboratory Tests Positive direct C… [Excerpted — this section continues on DailyMed.]

PRECAUTIONS General Prescribing Ceftriaxone 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. Although transient elevations of BUN and serum creatinine have been observed, at the recommended dosages, the nephrotoxic potential of Ceftriaxone Injection is similar to that of other cephalosporins. Ceftriaxone is excreted via both biliary and renal excretion (see CLINICAL PHARMACOLOGY ).

Therefore, patients with mild to moderate renal impairment normally require no adjustment in dosage when usual doses of Ceftriaxone 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 Injection dosage should not exceed 2 gm daily. Ceftriaxone has been associated with a fall in prothrombin activity.

Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated. Prolonged use of Ceftriaxone 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. Ceftriaxone Injection 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 ceftriaxone; 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 ceftriaxone and institution of conservative management. Therefore, Ceftriaxone Injection 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 ceftriaxone.

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 related biliary precipitation cannot be ruled out. Information for Patients Advise patients that neurological adverse reactions could occur with Ceftriaxone Injection use.

Instruct patients or their caregivers to inform their healthcare provider at once of any neurological signs and symptoms, including encephalopathy (disturbance of consciousness including somnolence, lethargy, and confusion), seizures, myoclonus, and nonconvulsive status epilepticus, for immediate treatment, or discontinuation of Ceftriaxone Injection (see WARNINGS AND PRECAUTIONS ). Patients should be counseled that antibacterial drugs including Ceftriaxone Injection should only be used to treat bacterial infections.

They do not treat viral infections ( e.g. , the common cold). When Ceftriaxone Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria… [Excerpted — this section continues on DailyMed.]