NEODOSE

INDICATIONS

• Gonococcal Infections: Recommended for the treatment of gonococcal ophthalmia neonatorium, disseminated gonococcal infection, gonococcal scalp abscess, and presumptive gonococcal infection in neonates born to mothers with untreated gonorrhea and at a high risk for infection. A single dose of ceftriaxone is also effective for ophthalmia neonatorum prophylaxis when erythromycin ointment is not available.
• Infective Endocarditis: The following recommendations are based on a consensus of experts . The full pediatric guidelines can be found here:

• Meningitis: Treatment of neonatal meningitis caused by susceptible gram-negative organisms (e.g. E coli, Pseudomonas, Klebsiella, H influenzae). CefTRIAXone is contraindicated due to the risk of kernicterus in neonates
• Sepsis: Treatment of neonatal sepsis caused by susceptible gram-negative organisms (e.g. E coli,Pseudomonas, Klebsiella, H influenzae). Optimal treatment for suspected, early-onset sepsis is broad-spectrum antimicrobial coverage using a combination of ampicillin and an aminoglycoside (usually gentamicin); once apathogen is identified, therapy should be narrowed unless synergism is required.CefTRIAXone is contraindicated due to the risk of kernicterus in neonates. There was no difference in failure rate between a 7-day vs 10-day duration of empirictreatment with IV cefTRIAXone and amikacin for culture-proven sepsis in 132 neonates, 1.5kg or more and gestational age 32 weeks or more, who remitted clinically by day 5 in arandomized study. The follow-up period was 28 days. The median age at presentation was 3days (2 to 4 days) and 56.8% had early-onset sepsis. The majority of organisms in bloodcultures were Klebsiella spp. (40.9%), Staphylococcus aureus (22.7%), Enterobacter spp.(16.7%), and MRSA (7.6%)

CONTRAINDICATIONS

• Contraindicated in premature neonates.
• Contraindicated for use in neonates with hyperbilirubinemia. Displaces bilirubin from albumin binding sites, resulting in higher free bilirubin serum concentrations.
• Concurrent administration of cefTRIAXone andIV calcium-containing solutions (including parenteral nutrition) or products in neonates is contraindicated. There have been a small number of fatal cases of cardiorespiratory arrest in young infants, with 6 deaths, associated with concurrent administration of cefTRIAXone and calciumcontaining intravenous solutions. In all cases, the cefTRIAXone dose (150 to 200 mg/kg/day) significantly exceeded the FDA recommended dose and/or was administered IV push. Crystalline material was noted in vascular beds on autopsy (lungs and kidneys) in 4 of the 5 infants for which results were available.
• Lidocaine added to IV cefTRIAXone solutions is contraindicated.

PRECAUTIONS

• Serious and occasionally fatal hypersensitivity reactions have occurred.
• Clostridium difficile associated diarrhea has been reported.
• Hematologic:
  • Methemoglobinemia has been reported; risk factors are glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites.
  • Prothrombin time alteration in patients with impaired vitamin K synthesis or low vitamin.
• Renal / Hepatic:
  • Presence of both hepatic dysfunction and renal disease.
  • Pediatric patients are at a greater risk of gallbladder pseudolithiasis (ceftriaxone-calcium precipitates).
  • Pediatric patients are at a greater risk of ceftriaxone-calcium precipitates in the urinary tract, which may present as urolithiasis, and ureteral obstruction and post-renal acute renal failure.
  • biliary stasis and biliary sludge risk factors, such as preceding major therapy, severe illness, and total parenteral nutrition; increased risk of pancreatitis, possibly secondary to biliary obstruction

ADVERSE EFFECTS

Eosinophilia, thrombocytosis, leukopenia. Increase in bleeding time. Diarrhea. Increase in BUN and serum creatinine. Increase in AST and ALT. Skin rash. Transient gallbladder precipitations occasionally associated with colicky abdominal pain, nausea, and vomiting. In a prospective cohort study (n=4579), third generation cephalosporins started by day 3 of life in extremely low birth weight infants (less than 1000 g) were associated with a significantly increased risk of candidiasis compared with other antibiotics.

ADMINISTRATION

Intravenous:

• Administer over 60 minutes at a concentration of 10 to 40 mg/mL (lower concentrations may be used, if necessary).
• Do not mix with calcium-containing solutions in the same IV line; precipitation may occur.
• Avoid administration of calcium-containing solutions or products within 48 hours of the last administration of cefTRIAXone.
• Intermittent IV infusion over 30 minutes at a concentration of 1 to 40 mg/mL as well as 50 mg/mL.

Intramuscular:

• To reduce pain at the injection site, reconstitute with 1% lidocaine without epinephrine to a final concentration of 250 mg/mL or 350 mg/mL.

MONITORING

Monitor prothrombin time in high risk patients (eg, chronic hepatic disease and malnutrition). Frequently monitor coagulation parameters during concomitant vitamin K antagonist therapy. Monitor for signs and symptoms of gallbladder disease. CBC for eosinophilia, thrombocytosis, leukopenia. Serum electrolytes, BUN, creatinine. AST, ALT, bilirubin. Consider abdominal ultrasonography..