ceftriaxone (Rx)

>10%

Induration after IM injection (5-17%)

1-10%

Eosinophilia (6%)

Thrombocytosis (5%)

Diarrhea (3%)

Elevated hepatic transaminases (3%)

Leukopenia (2%)

Rash (2%)

Increased blood urea nitrogen (BUN) (1%)

Induration at IV site (1%)

Pain (1%)

<1%

Agranulocytosis

Anaphylaxis

Anemia

Basophilia

Bronchospasm

Candidiasis

Chills

Diaphoresis

Dizziness

Dysgeusia

Flushing

Gallstones

Glycosuria

Headache

Hematuria

Hemolytic anemia

Increased alkaline phosphatase or bilirubin

Increased creatinine

Jaundice

Leukocytosis

Lymphocytosis

Lymphopenia

Monocytosis

Nausea

Neutropenia

Phlebitis

Prolonged or decreased prothrombin time (PT)

Pruritus

Renal stones

Serum sickness

Thrombocytopenia

Urinary casts

Vaginitis

Vomiting

Postmarketing reports

Pancreatitis, stomatitis and glossitis

Oliguria, ureteric obstruction, post-renal acute renal failure

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)

Convulsion

Contraindications

Documented hypersensitivity; hyperbilirubinemic neonates, particularly those who are premature; neonates <28 days if they receive calcium-containing IV products

Intravenous administration of ceftriaxone solutions containing lidocaine

Lidocaine contraindications if lidocaine solution used as solvent with ceftriaxone for intramuscular injection

Concomitant calcium-ceftriaxone administration

• Risk of fatal calcium-ceftriaxone precipitant formation in lungs and kidneys of term and preterm neonates
• <28 days: Do not give any calcium-containing IV drugs or products within 48 hours of ceftriaxone (within 5 days if neonate is <10 days, per Health Canada)
• >28 days: Calcium may be given in sequence after ceftriaxone once infusion line has been flushed, but not simultaneously in same bag or line (chemically incompatible)

Cautions

10-g pharmacy bulk package should not be used for direct infusion

Immune-mediated hemolytic anemia reported; if patient develops anemia while on ceftriaxone, stop antibiotic until etiology determined; severe hemolytic anemia, including fatalities, reported in both adults and children

May increase INR, especially in nutritionally deficient patients, hepatic or renal disease or prolonged treatment

Dosage must be adjusted in severe renal insufficiency (high dosages may cause CNS toxicity)

Superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy

Use with caution in patients with history of penicillin allergy

Use with caution in patients with history of GI disease, especially colitis

Use with caution in breast-feeding women; drug may displace bilirubin from albumin-binding sites, increasing risk of kernicterus

Abnormal gallbladder sonograms reported, possibly the result of ceftriaxone-calcium precipitates; discontinue if signs or symptoms of gallbladder diseease occur

Ceftriaxone-calcium precipitates in urinary tract observed in patients receiving ceftriaxone; may be detected as sonographic abnormalities; patients may be asymptomatic or may develop symptoms of urolithiasis, and ureteral obstruction and post-renal acute renal failure; appears to be reversible upon discontinuation of therapy and institution of appropriate management; ensure adequate hydration; discontinue therapy in patients who develop signs and symptoms suggestive of urolithiasis, oliguria or renal failure and/or the sonographic findings

Clostridium difficile-associated diarrhea (CDAD reported with use of nearly all antibacterial agents, including ceftriaxone; If CDAD suspected or confirmed, may consider discontinuing ongoing antibacterial use not directed against C. difficile; institute appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation

Pancreatitis secondary to biliary obstruction reported rarely; use with caution in patients with gallbladder, biliary tract, liver, or pancreatic disease and patients with history of penicillin hypersensitivity

Inform patients that use of local anesthetics may cause methemoglobinemia, which must be treated promptly; advise patients or caregivers to stop use and seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue

Use with caution in patients with history of GI disease (eg, colitis)

Pregnancy category: B

Lactation: Drug enters breast milk in low concentrations; use with caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Third-generation cephalosporin with broad-spectrum gram-negative activity; has lower efficacy against gram-positive organisms but higher efficacy against resistant organisms; highly stable in presence of beta-lactamases (penicillinase and cephalosporinase) of gram-negative and gram-positive bacteria; bactericidal activity results from inhibiting cell-wall synthesis by binding to 1 or more penicillin-binding proteins; exerts antimicrobial effect by interfering with synthesis of peptidoglycan (major structural component of bacterial cell wall); bacteria eventually lyse because activity of cell-wall autolytic enzymes continues while cell-wall assembly is arrested

Absorption

IM preparation well absorbed

Peak plasma time: 2-3 hr (IM)

Distribution

Distributed throughout body, including gallbladder, lungs, bone, bile, and CSF (higher concentrations achieved when meninges are inflamed); crosses placenta; enters amniotic fluid and breast milk

Protein bound: 85-95%

Vd: 6-14 L

Metabolism

Metabolized in liver

Elimination

Half-life: 5-9 hr (normal hepatic and renal function); 12-16 hr (mild-to-severe renal impairment)

Excretion: Urine (33-67% as unchanged drug), feces

IV Incompatibilities

Solution: LR (at drug concentrations >10 mg/mL; compatible at 1 mg/mL)

Additive: Aminophylline, clindamycin, linezolid, theophylline, metronidazole (at metronidazole 15 g/L with ceftriaxone 20 g/L; compatible at metronidazole 7.5 g/L with ceftriaxone 10 g/L)

Syringe: Lidocaine (variable)

Y-site: Alatrofloxacin, amphotericin B cholesteryl sulfate, amsacrine, filgrastim, fluconazole, labetalol, pentamidine, vinorelbine, vancomycin

General: Calcium-containing drugs

IV/IM Preparation

Dilutions are stable for 24 hours at room temperature

IV

• Reconstitute to ~100 mg/mL, then dilute further to 10-40 mg/mL
• 10 g bulk package: not for direct IV infusion; reconstitute in 95 mL, then use appropriate portions for further dilution
• 10-g bulk package not for direct IV injection; reconstitute in 95 mL, then use appropriate portions for further dilution

IM

• Dilute with compatible fluid (eg, SWI, NS, D5W) to 250-350 mg/mL

IV/IM Administration

IV: Infuse intermittently over 30 minutes

IM: Inject deep into large muscle mass