Ceftriaxone injection

Use the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not use a double dose to make up for a missed one.

Do not use ceftriaxone in a child without a doctor's advice, and never give more than the child's prescribed dose. Ceftriaxone injection can be dangerous when given to a newborn baby with any intravenous medicines that contain calcium, including total parental nutrition (TPN). Ceftriaxone should never be used in a premature baby, or in any newborn baby who has jaundice.

You should not use this medicine if you are allergic to ceftriaxone or to other cephalosporin antibiotics, such as:

• cefaclor (Raniclor);

• cefadroxil (Duricef);

• cefazolin (Ancef);

• cefdinir (Omnicef);

• cefditoren (Spectracef);

• cefpodoxime (Vantin);

• cefprozil (Cefzil);

• ceftibuten (Cedax);

• cefuroxime (Ceftin);

• cephalexin (Keflex); or

• cephradine (Velosef).

To make sure ceftriaxone is safe for you, tell your doctor if you have:

• an allergy to any drugs (especially penicillins);

• kidney disease (or if you are on dialysis);

• liver disease;

• diabetes;

• gallbladder disease;

• a stomach or intestinal disorder such as colitis;

• poor nutrition; or

• a condition for which you take a blood thinner (warfarin, Coumadin, Jantoven).

Ceftriaxone is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Ceftriaxone can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Other drugs may interact with ceftriaxone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

250 mg IM as a single dose

Uses: For the treatment of uncomplicated cervical/urethral and rectal gonorrhea due to Neisseria gonorrhoeae (including penicillinase- and nonpenicillinase-producing strains) and pharyngeal gonorrhea due to nonpenicillinase-producing strains of N gonorrhoeae

US CDC Recommendations: 250 mg IM as a single dose

Comments:
-With azithromycin, the recommended regimen for uncomplicated infections of the pharynx, cervix, urethra, and rectum
-Preferable to administer this drug and azithromycin simultaneously and under direct observation
-Suspected treatment failures should first be retreated with the recommended regimen as reinfections more likely than treatment failures.
-The patient's sexual partner(s) should also be evaluated/treated.
-Current guidelines should be consulted for additional information.

1 to 2 g IV or IM once a day (or in equally divided doses twice a day)

Duration of therapy: 4 to 14 days
-Complicated infections: Longer therapy may be required.

Comments:
-Dose and duration depend on the nature and severity of the infection.
-The total daily dose should not exceed 4 g.
-This drug has been effective in a limited number of cases of meningitis and shunt infection due to S epidermidis and E coli.

Use: For the treatment of meningitis due to H influenzae, N meningitidis, or S pneumoniae

IDSA Recommendations:
-Bacterial meningitis: 4 g IV every 24 hours (or in equally divided doses every 12 hours) for 7 to at least 21 days

US CDC Recommendations:
-Gonococcal meningitis: 1 to 2 g IV every 12 to 24 hours for 10 to 14 days

Comments:
-Duration of bacterial meningitis therapy should be based on isolated pathogen.
-With azithromycin, the recommended regimen for gonococcal meningitis; the patient's sexual partner(s) should also be evaluated/treated.
-Current guidelines should be consulted for additional information.

1 to 2 g IV or IM once a day (or in equally divided doses twice a day)

Duration of therapy: 4 to 14 days
-Complicated infections: Longer therapy may be required.

Comments:
-Dose and duration depend on the nature and severity of the infection.
-The total daily dose should not exceed 4 g.
-This drug has no activity against Chlamydia trachomatis; appropriate antichlamydial therapy should be added when C trachomatis is a suspected pathogen.

Use: For the treatment of pelvic inflammatory disease (PID) due to N gonorrhoeae

US CDC Recommendations: 250 mg IM as a single dose

Comments:
-Part of a recommended IM/oral regimen for acute PID (of mild to moderate severity); this drug should be used with doxycycline (with or without metronidazole).
-Patients not responding to IM/oral therapy within 72 hours should be reevaluated to confirm diagnosis and should receive IV therapy.
-The patient's sexual partner(s) should also be evaluated/treated.
-Current guidelines should be consulted for additional information.

1 to 2 g IV or IM once a day (or in equally divided doses twice a day)

Duration of therapy: 4 to 14 days
-Complicated infections: Longer therapy may be required.
-Infections due to S pyogenes: At least 10 days

Comments:
-Dose and duration depend on the nature and severity of the infection.
-The total daily dose should not exceed 4 g.

Uses: For the treatment of skin and skin structure infections due to S aureus, S epidermidis, S pyogenes, viridans group streptococci, E coli, E cloacae, K oxytoca, K pneumoniae, P mirabilis, M morganii, Pseudomonas aeruginosa, S marcescens, Acinetobacter calcoaceticus, B fragilis, or Peptostreptococcus species

IDSA Recommendations:
-Incisional surgical site infection: 1 g IV every 24 hours
-Aeromonas hydrophila necrotizing infection: 1 to 2 g IV every 24 hours
-Vibrio vulnificus necrotizing infection: 1 g IV once a day
-Infection after animal bite: 1 g IV every 12 hours

Comments:
-Recommended for use with metronidazole as a combination regimen for treatment of incisional surgical site infections after intestinal or genitourinary tract surgery.
-Recommended for use with metronidazole for treatment of incisional surgical site infections after surgery of axilla or perineum; coverage for methicillin-resistant S aureus may be needed.
-In combination with doxycycline, recommended as a preferred IV drug for the treatment of necrotizing infections of the skin, fascia, and muscle due to A hydrophila or V vulnificus
-Current guidelines should be consulted for additional information.

1 g IV as a single dose 30 to 120 minutes before surgery

Comments:
-Preoperative use of this drug may reduce the incidence of postoperative infections in patients undergoing surgical procedures classified as contaminated or potentially contaminated (e.g., vaginal or abdominal hysterectomy, cholecystectomy for chronic calculous cholecystitis in high-risk patients [such as those older than 70 years] with acute cholecystitis not requiring therapeutic antimicrobials, obstructive jaundice, common duct bile stones) and in surgical patients for whom infection at the operative site would present serious risk (e.g., during coronary artery bypass surgery).
-This drug shown to be as effective as cefazolin to prevent infection after coronary artery bypass surgery; no placebo-controlled trials to evaluate any cephalosporin preventing infection after coronary artery bypass surgery.

American Society of Health-System Pharmacists (ASHP), IDSA, SIS, and Society for Healthcare Epidemiology of America (SHEA) Recommendations:
-Preoperative dose: 2 g IV as a single dose, starting within 60 minutes before surgical incision

Comments:
-A single prophylactic dose is usually sufficient; if prophylaxis is continued postoperatively, duration should be less than 24 hours.
-Readministration may be needed for unusually long procedures to ensure adequate serum and tissue drug levels.
-Redosing may be needed if drug half-life is shortened (e.g., extensive burns) or if prolonged/excessive bleeding during surgery; redosing may not be needed if drug half-life is prolonged (e.g., renal dysfunction).
-Current guidelines should be consulted for additional information.

Uses: For surgical prophylaxis for the following procedures:
-Biliary tract (recommended regimen): Open procedure and elective, high-risk laparoscopic procedure; should limit to patients requiring antimicrobial therapy for acute cholecystitis or acute biliary tract infections (which may not be established before incision), not patients undergoing cholecystectomy for noninfected biliary conditions (including biliary colic or dyskinesia without infection)
-Colorectal (with metronidazole, as a recommended regimen)

US CDC Recommendations: 250 mg IM as a single dose

Comments:
-With azithromycin and (metronidazole or tinidazole), the recommended regimen for presumptive therapy after sexual assault
-Current guidelines should be consulted for additional information.

1 month or older: 50 to 75 mg/kg IV or IM once a day (or in equally divided doses twice a day)
Maximum dose: 2 g/day

Uses: For the treatment of serious miscellaneous infections when due to susceptible organisms; may include:
-Bacterial septicemia due to S aureus, S pneumoniae, E coli, H influenzae, or K pneumoniae
-Bone and joint infections due to S aureus, S pneumoniae, E coli, P mirabilis, K pneumoniae, or Enterobacter species
-Urinary tract infections due to E coli, P mirabilis, P vulgaris, M morganii, or K pneumoniae

American Academy of Pediatrics (AAP) Recommendations:
Neonates: 50 mg/kg IV or IM every 24 hours

1 month or older:
Mild to moderate infections: 50 to 75 mg/kg IV or IM once a day
Maximum dose: 1 g/day

Severe infections: 100 mg/kg IV or IM once a day (or in equally divided doses twice a day)
Maximum dose: 2 to 4 g/day

Comments:
-Neonates should not receive this drug IV if they are receiving (or expected to receive) calcium-containing IV solutions (including parenteral nutrition).
-In patients at least 1 year of age, larger doses (up to 100 mg/day) appropriate for penicillin-resistant pneumococcal pneumonia.
-Current guidelines should be consulted for additional information.

50 mg/kg IM as a single dose
Maximum dose: 1 g/dose

Uses: For the treatment of acute bacterial otitis media due to S pneumoniae, H influenzae (including beta-lactamase producing strains), or Moraxella catarrhalis (including beta-lactamase producing strains)

AAP Recommendations:
1 month or older: 50 mg/kg IM once a day
Maximum dose: 1 g/dose
Duration of therapy: 1 to 3 days

AAN and IDSA Recommendations: 50 to 75 mg/kg IV once a day
Maximum dose: 2 g/day
Duration of therapy: 14 days

Comments:
-IDSA recommends this drug as the preferred parenteral regimen for early neurologic disease (meningitis or radiculopathy), cardiac disease, and late disease (recurrent arthritis after oral regimen, central or peripheral nervous system disease).
-Duration of therapy has ranged from 10 to 28 days.
-Current guidelines should be consulted for additional information.

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-infected Adolescents: 1 g IV every 24 hours

Duration of Salmonellosis Therapy:
For gastroenteritis without bacteremia:
-If CD4 count at least 200 cells/mm3: 7 to 14 days
-If CD4 count less than 200 cells/mm3: 2 to 6 weeks

For gastroenteritis with bacteremia:
-If CD4 count at least 200 cells/mm3: 14 days; longer if persistent bacteremia or complicated infection (e.g., metastatic foci of infection present)
-If CD4 count less than 200 cells/mm3: 2 to 6 weeks

Comments:
-Recommended as alternative empiric therapy for bacterial enteric infections (pending diagnostic studies) and as alternative therapy for salmonella gastroenteritis with or without bacteremia
-Empiric therapy for bacterial enteric infections recommended for patients with advanced HIV (CD4 count less than 200 cells/mm3 or concomitant AIDS-defining illnesses) and clinically severe diarrhea (at least 6 stools/day or bloody stool) and/or associated fever/chills. Fecal samples should be obtained for diagnostic testing before starting therapy; therapy should be adjusted based on those results.
-All HIV-infected patients with salmonellosis should receive antibiotic therapy; increased risk of bacteremia (by 20- to 100-fold) and mortality (by up to 7-fold) compared to HIV-negative subjects.
-Current guidelines should be consulted for additional information.

US CDC Recommendations:
Neonates: 25 to 50 mg/kg IV or IM as a single dose
Maximum dose: 125 mg/dose

Comments:
-The recommended regimen for gonococcal ophthalmia neonatorum
-An infectious disease specialist should be consulted.
-This drug should be used with caution in hyperbilirubinemic neonates, especially if premature.
-Current guidelines should be consulted for additional information.

Renal dysfunction alone: No adjustment recommended.

Significant renal dysfunction plus liver dysfunction: Caution recommended; dose should not exceed 2 g/day.

Comments:
-No adjustment normally needed when standard doses are used in patients with renal failure.
-Close clinical monitoring for safety and efficacy recommended for patients with both severe renal and liver dysfunction.

Administration advice:
-May administer IV or IM
-IM: Inject well within body of relatively large muscle; aspiration helps avoid accidental injection into a blood vessel.
-IV: Administer by IV infusion over 30 minutes (except in neonates); in neonates, administer over 60 minutes to reduce risk of bilirubin encephalopathy.
-Do not administer simultaneously with IV solutions containing calcium, including continuous calcium-containing infusions (e.g., parenteral nutrition) via a Y-site.
-In patients other than neonates, may administer this drug and calcium-containing IV solutions sequentially if infusion lines are thoroughly flushed with a compatible fluid between infusions
-Duplex(R) container: Do not use plastic containers in series connections.
-In general, continue this drug for at least 2 days after signs/symptoms of infection have disappeared; usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required; when treating infections due to S pyogenes, continue therapy for at least 10 days.
-If vancomycin, amsacrine, aminoglycosides, or fluconazole need to be used concomitantly with this drug by intermittent IV infusion, administer sequentially and use a compatible fluid to thoroughly flush IV line between administrations

Storage requirements:
-Duplex(R) container: Store unactivated unit folded (until activation intended) at 20C to 25C (68F to 77F), excursion permitted to 15C to 30C (59F to 86F); do not freeze; after reconstitution (activation), use within 24 hours if stored at room temperature or within 7 days if stored under refrigeration.
-Powder (prior to reconstitution): Store at room temperature (25C [77F]) or below; protect from light.
-Solutions (after reconstitution): The manufacturer product information should be consulted; do not refreeze frozen solutions.

Reconstitution/preparation techniques:
-The manufacturer product information should be consulted.
-IM: The maximum concentration for IM injection is 350 mg/mL; may dilute with 1% lidocaine
-IV: Diluents containing calcium (e.g., Ringer's solution, Hartmann's solution) should not be used to reconstitute vials of this drug or further dilute a reconstituted vial for IV use (precipitate can form).

IV compatibility:
-Duplex(R) container: Compatible fluids for flushing IV lines: 0.9% sodium chloride injection, 5% dextrose in water
-Duplex(R) container: Do not introduce additives into the container.
-Vials: Compatible diluents (at room temperature, at concentrations between 10 and 40 mg/mL): Sterile water (glass or polyvinyl chloride [PVC] container), 0.9% sodium chloride solution (glass or PVC container), 5% dextrose solution (glass or PVC container), 10% dextrose solution (glass or PVC container), 5% dextrose and 0.9% sodium chloride solution (PVC container), 5% dextrose and 0.45% sodium chloride solution (glass or PVC container), sodium lactate (PVC container), 10% invert sugar (glass container), 5% sodium bicarbonate (glass container), FreAmine(R) III (glass container), Normosol-M in 5% dextrose (glass or PVC container), Ionosol-B in 5% dextrose (glass container), 5% mannitol (glass container), 10% mannitol (glass container)
-Vials: Compatibility with metronidazole shown; concentration should not exceed 5 to 7.5 mg/mL metronidazole with ceftriaxone 10 mg/mL as an admixture. Metronidazole at concentrations greater than 8 mg/mL will precipitate.
-Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible.
-Should not physically mix with or piggyback into solution containing other antimicrobial drugs or into diluent solutions other than those listed (due to possible incompatibility)
-Precipitation of ceftriaxone-calcium can occur when this drug is mixed with calcium-containing solutions in the same IV line.
-The manufacturer product information should be consulted.

General:
-To reduce the development of drug-resistant organisms and maintain effective therapy, antibiotics should be used only to treat or prevent infections proven or strongly suspected to be caused by susceptible bacteria.
-Culture and susceptibility information should be considered when selecting/modifying antibacterial therapy or, if no data are available, local epidemiology and susceptibility patterns may be considered when selecting empiric therapy.
-Appropriate culture and susceptibility testing recommended before therapy to isolate and identify infecting organisms and to establish susceptibility to this drug. Therapy may be started before test results are known; appropriate therapy should be continued when results are available.
-If C trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added as this drug has no activity against the organism.
-The IV route is preferred for severe or life-threatening infections and for patients with reduced resistance (e.g., malnutrition, trauma, surgery, heart failure, malignancy, shock).

Monitoring:
-Hematologic: Prothrombin time in patients with impaired vitamin K synthesis or low vitamin K stores
-Renal: Renal function in elderly patients

Patient advice:
-Avoid missing doses and complete the entire course of therapy.

Animal studies have failed to reveal evidence of embryotoxicity, fetotoxicity, or teratogenicity. This drug crosses the placenta. There are no controlled data in human pregnancy. AU TGA pregnancy category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

This drug should be used during pregnancy only if clearly needed and the benefit outweighs the risk. AU TGA pregnancy category: B1 US FDA pregnancy category: B

Summary of Use during Lactation

Ceftriaxone is acceptable to use during breastfeeding. Limited information indicates that maternal doses of ceftriaxone of 1 gram produce low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally, disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush, has been reported with cephalosporins, but these effects have not been adequately evaluated.

Drug Levels

Maternal Levels. Following administration of a 1 gram dose of ceftriaxone intramuscularly or intravenously on day 3 postpartum to 20 women, peak milk levels averaged about 0.7 and 0.5 mg/L, respectively.[1] Peaks occurred about 4 hours after the dose and fell very slowly over 24 hours with half-lives of 13 to 17 hours. The amounts in milk represent an infant dosage of about 0.5% of the maternal weight-adjusted dosage. The infant would be expected to ingest only a few milligrams of ceftriaxone per day with usual doses.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

A mother who was exclusively nursing her 52-day-old infant developed a soft-tissue infection. She was treated with intravenous teicoplanin 400 mg every 12 hours for 3 doses, then 400 mg daily for 5 days total, intravenous ceftriaxone 1 gram daily, topical mupirocin cream twice daily. A careful follow-up indicated that her infant had no adverse effects.[2]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

References

1. Kafetzis DA, Brater DC, Fanourgakis JE et al. Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk postpartum. Antimicrob Agents Chemother. 1983;23:870-3. PMID: 6311089

2. Kaplan YC, Keskin-Arslan E, Acar S et al. Teicoplanin use during breastfeeding. Breastfeed Med. 2017. PMID: 28051878