Dosing and uses of Rocephin (ceftriaxone)
Adult dosage forms and strengths
injectable solution
- 1g/50mL
- 2g/50mL
powder for injection
- 250mg
- 500mg
- 1g
- 2g
- 10g
- 100g
Intra-abdominal Infections
Complicated, mild-to-moderate, community acquired: 1-2 g/day IV in single daily dose or divided q12hr for 4-7 days, in combination with metronidazole
Acute Bacterial Otitis Media
50 mg/kg IM once
Persistent or treatment failures: 50 mg/kg IV/IM for 3 days
Pelvic Inflammatory Disease
250 mg IM as single dose with doxycycline, with or without metonidazole for 14 days
Septic/toxic Shock (Off-label)
2 g IV once daily; with clindamycin for toxic shock
Skin and Soft Necrotizing Infection (Off-label)
Due to Aeromonas hydrophilia: 1-2 g IV qDay in combination with doxycycline
Due to Vibrio vulnificus; 1 g IV qDay in combination with doxycycline
Continue treatment until further debridement not necessary, clinical improvement observed, and patient is afebrile for 48-72 hr
Severe Acute Bacterial Rhinosinusitis (Off-label)
Infection requiring hospitalization: 1-2 g IV q12-24hr for 5-7 days
Prosthetic Joint Infection
2 g IV q24hr for 2-6 weeks; continue treatment until clinical improvement observed and patient is afebrile for 48-72 hr
Meningitis
2 g IV q12hr for 7-14 days
Acute Uncomplicated Pyelonephritis
1-2 g IV qDay
Surgical Prophylaxis
Prophylaxis of surgical infection
1 g IV 0.5-2 hours before procedure
Uncomplicated Gonococcal Infections
Uncomplicated gonococcal infection of pharynx, cervix, urethra, or rectum: ceftriaxone 250 mg IM once plus azithromycin 1 g PO once (preferred) or alternatively, doxycycline 100 mg PO q12hr for 7 days
CDC STD guidelines: MMWR Recomm Rep. June 5, 2015:64(RR3);1-137
Sexual assault
- Prophylaxis of sexually transmitted diseases (STDs) such as gonorrhea after sexual assault per CDC guidelines includes the following 3-drug regimen:
- Ceftriaxone 250 mg IM once, PLUS
- Azithromycin 1 g PO once, PLUS
- Metronidazole or tinidazole 2 g PO once
- If alcohol has been recently ingested or emergency contraception is provided, metronidazole or tinidazole can be taken by the victim at home rather than as directly observed therapy to avoid drug interactions
Other Gonococcal Infections (Off-label)
Gonococcal conjunctivitis: 1 g IM once
Disseminated gonococcal infection: 1 g/day IV/IM; continued for at least 24-48 hours after improvement is observed, then continued with cefixime 400 mg PO q12hr to complete at least 1 week of therapy
Gonococcal endocarditis:1-2 g IV q12hr for 4 weeks
Gonococcal meningitis: 1-2 g IV q12hr for 10-14 days
Acute epdidymitis: 250 mg IM once with doxycycline
Dosing Considerations
Susceptible organisms
- Anaerobic cocci, Bacteroides fragilis, Borrelia burgdorferi, Clostridium spp, Enterobacter spp, Escherichia coli, Haemophilus influenzae, Klebsiella spp, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Proteus mirabilis, Providencia rettgeri, Pseudomonas spp, Serratia spp, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes
Pediatric dosage forms and strengths
injectable solution
- 1g/50mL
- 2g/50mL
powder for injection
- 250mg
- 500mg
- 1g
- 2g
Acute Bacterial Otitis Media
50 mg/kg IM in single dose; not to exceed 1 g
Epiglottis (Off-label)
100 mg/kg/day IV on first day; follow with 50 mg/kg on day 2 or 75 mg/kg qDay for 10-14 days
Meningitis
100 mg/kg/day IV/IM in single daily dose or divided q12hr for 7-14 days; not to exceed 4 g/day
Serious Infections Other Than Meningitis
50-75 mg/kg/day IV/IM divided q12hr for 7-14 days
Acute Epdidymitis (Off-label)
>8 years and >45 kg: 250 mg IM once with concomitant doxycycline regimen
Skin/Skin Structure Infections
>12 years: 1-2 g/day IV/IM in single daily dose or divided q12hr for 7-14 days, depending on type and severity of infection
Gonococcal Infections
Neonates
- Ophthalmia neonatorum: 25-50 mg/kg IV/IM once; not to exceed 125 mg
- Disseminated gonococcal infections and gonococcal scalp abscesses: 25-50 mg/kg/day IV/IM in single daily dose for 7 days; if meningitis is documented, treat for 10-14 days
- Prophylaxis for infants of mothers with gonococcal infection: 25-50 mg/kg IV/IM once; not to exceed 125 mg
Children
- <45 kg with uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis: 125 mg IM once
- <45 kg with bacteremia or arthritis: 50 mg/kg/day IM/IV in single daily dose for 7 days; daily dose not to exceed 1 g
- >45 kg with bacteremia or arthritis: 50 mg/kg/day IM/IV in single daily dose for 7 days
- >45 kg: 1-2 g IV q12hr
Rocephin (ceftriaxone) adverse (side) effects
>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
Warnings
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
Use with caution in patients with history of GI disease (eg, colitis)
Pregnancy and lactation
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.
Pharmacology of Rocephin (ceftriaxone)
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
Administration
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
