cephalosporins—third generation

Contraindicated in:

Hypersensitivity to cephalosporins;
Serious hypersensitivity to penicillins;
Pedi: Premature neonates up to a postmenstrual age of 41 wk (ceftriaxone only);
Pedi: Hyperbilirubinemic neonates (may lead to bilirubin encephalopathy);
Pedi: Neonates ≤28 days requiring calcium-containing IV solutions (↑ risk of precipitation formation).

Use Cautiously in:

Renal impairment (↓ dosing/↑ dosing interval recommended for: cefdinir if CCr <30 mL/min, cefixime if CCr ≤60 mL/min, cefotaxime if CCr <20 mL/min, cefpodoxime if CCr <30 mL/min, ceftazidime if CCr ≤50 mL/min);
Combined severe hepatic and renal impairment (↑ risk of neurological adverse reactions with ceftriaxone; dose ↓/↑ dosing interval recommended);
Diabetes (cefdinir suspension contains sucrose);
Phenylketonuria (cefixime chewable tablets contain aspartame);
History of GI disease, especially colitis;
Pedi: ↑risk of urolithiasis and acute renal failure (ceftriaxone only);
Geri: Dose adjustment due to age-related ↓ in renal function may be necessary.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, STEVENS-JOHNSON SYNDROME (SJS), urticaria

GI: diarrhea, nausea, vomiting, cholelithiasis (ceftriaxone), CLOSTRIDIOIDES DIFFICILE ASSOCIATED DIARRHEA (CDAD), cramps, pancreatitis (ceftriaxone)

GU: acute renal failure (ceftriaxone), hematuria, urolithiasis (ceftriaxone), vaginal moniliasis

Hemat: agranulocytosis, bleeding, eosinophilia, hemolytic anemia, lymphocytosis, neutropenia, thrombocytopenia, thrombocytosis

Local: pain at IM site, phlebitis at IV site

Neuro: encephalopathy, headache, SEIZURES (HIGH DOSES)

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND SERUM SICKNESS), superinfection

Interactions ⬆ ⬇

Drug-drug:

Probenecid↓ excretion and ↑ serum levels (cefdinir, cefixime, cefotaxime, cefpodoxime, ceftriaxone).
Concurrent use of loop diuretics, aminoglycosides, or NSAIDs may ↑ risk of nephrotoxicity.
Antacids↓ absorption of cefdinir and cefpodoxime.
Iron supplements↓ absorption of cefdinir.
H2-receptor antagonists↓ absorption of cefpodoxime.
Cefixime may ↑ carbamazepine levels.
Ceftriaxone should not be administered concomitantly with any calcium-containing solutions.
Ceftriaxone may ↑ risk of bleeding with warfarin.

Availability ⬆ ⬇

Cefdinir

(Generic available)

Capsules: 300 mg
Oral suspensionstrawberry: 125 mg/5 mL; 250 mg/5 mL

Cefixime

(Generic available)

Capsules: 400 mg
Chewable tablets (contain aspartame): 100 mg; 150 mg; 200 mg
Oral suspensionstrawberry: 100 mg/5 mL; 200 mg/5 mL; 500 mg/5 mL
Tablets: 400 mg

Cefotaxime

(Generic available)

Powder for injection: 500 mg/vial; 1 g/vial; 2 g/vial; 10 g/vial

Cefpodoxime

(Generic available)

Oral suspension (lemon creme: 50 mg/5 mL; 100 mg/5 mL
Tablets: 100 mg; 200 mg

Ceftazidime

(Generic available)

Powder for injection: 1 g/vial; 2 g/vial; 6 g/vial
Premixed infusion: 1 g/50 mL; 2 g/50 mL

Ceftriaxone

(Generic available)

Powder for injection: 250 mg/vial; 500 mg/vial; 1 g/vial; 2 g/vial; 10 g/vial; 100 g/vial
Premixed infusion: 1 g/50 mL; 2 g/50 mL

Route/Dosage ⬆ ⬇

Cefdinir

PO (Adults ≥13 yr): 300 mg every 12 hr or 600 mg every 24 hr (use every 12 hr dosing only for community-acquired pneumonia or skin and skin structure infections).
PO (Children 6 mo–12 yr): 7 mg/kg every 12 hr (use only for skin/skin structure infections) or 14 mg/kg every 24 hr; dose should not exceed 600 mg/day.

Renal Impairment

PO (Adults and Children ≥13 yr): CCr <30 mL/min: 300 mg every 24 hr.

Renal Impairment

PO (Children 6 mo–12 yr): CCr <30 mL/min: 7 mg/kg every 24 hr.

Cefixime

PO (Adults and Children >12 yr or >45 kg): Most infections: 400 mg once daily; Gonorrhea: 400 mg single dose.
PO (Children 6 mo–12 yr): 8 mg/kg once daily or 4 mg/kg every 12 h.

Renal Impairment

PO (Adults ): CCr 21–60 mL/min: 75% of standard dose once daily; CCr ≤20 mL/min: 50% of standard dose once daily.

Cefotaxime

IM IV (Adults and Children >12 yr): Most uncomplicated infections: 1 g every 12 hr. Moderate or severe infections: 1–2 g every 6–8 hr. Life-threatening infections: 2 g every 4 hr (maximum dose = 12 g/day). Gonococcal urethritis/cervicitis or rectal gonorrhea in females: 500 mg IM (single dose). Rectal gonorrhea in males: 1 g IM (single dose). Perioperative prophylaxis: 1 g 30–90 min before initial incision (one-time dose).
IM IV (Children 1 mo–12 yr): <50 kg: 100–200 mg/kg/day divided every 6–8 hr. Meningitis: 200 mg/kg/day divided every 6 hr. Invasive pneumococcal meningitis: 225–300 mg/kg/day divided every 6–8 hr. ≥50 kg: see adult dosing.
IV (Neonates 1–4 wk): 50 mg/kg every 6–8 hr.
IV (Neonates ≤1 wk): 50 mg/kg every 8–12 hr.

Renal Impairment

(Adults ): CCr <20 mL/min:↓ dose by 50%.

Cefpodoxime

PO (Adults ): Most infections: 200 mg every 12 hr. Skin and skin structure infections: 400 mg every 12 hr. Urinary tract infections/pharyngitis: 100 mg every 12 hr. Gonorrhea: 200 mg single dose.
PO (Children 2 mo–12 yr): Pharyngitis/tonsillitis/otitis media/acute maxillary sinusitis: 5 mg/kg every 12 hr (not to exceed 200 mg/dose).

Renal Impairment

PO (Adults ): CCr <30 mL/min:↑ dosing interval to every 24 hr.

Ceftazidime

IM IV (Adults and Children ≥12 yr): Pneumonia and skin/skin structure infections: 500 mg–1 g every 8 hr. Bone and joint infections: 2 g every 12 hr. Severe and life-threatening infections: 2 g every 8 hr. Complicated urinary tract infections: 500 mg every 8–12 hr. Uncomplicated urinary tract infections: 250 mg every 12 hr. Cystic fibrosis lung infection caused by P. aeruginosa: 30–50 mg/kg every 8 hr (maximum dose = 6 g/day).
IM IV (Children 1 mo–12 yr): 33.3–50 mg/kg every 8 hr (maximum dose = 6 g/day).
IM IV (Neonates ≤4 wk): 50 mg/kg every 8–12 hr.

Renal Impairment

IM IV (Adults ): CCr 31–50 mL/min: 1 g every 12 hr; CCr 16–30 mL/min: 1 g every 24 hr; CCr 6–15 mL/min: 500 mg every 24 hr; CCr <5 mL/min: 500 mg every 48 hr.

Ceftriaxone

IM IV (Adults ): Most infections: 1–2 g every 12–24 hr. Gonorrhea: 250 mg IM (single dose). Meningitis: 2 g every 12 hr. Perioperative prophylaxis: 1 g 30–120 min before initial incision (single dose).
IM IV (Children ): Most infections: 25–37.5 mg/kg every 12 hr or 50–75 mg/kg every 24 hr; dose should not exceed 2 g/day. Meningitis: 100 mg/kg every 24 hr or 50 mg/kg every 12 hr; dose should not exceed 4 g/day. Acute otitis media: 50 mg/kg IM single dose; dose should not exceed 1 g. Uncomplicated gonorrhea: 125 mg IM (single dose).

Hepatic/Renal Impairment

IM IV (Adults ): Hepatic impairment with significant renal impairment: Not to exceed 2 g/day.

US Brand Names ⬆ ⬇

cefdinir: ~~Omnicef,~~

cefixime: ~~, Suprax,~~

cefotaxime: ~~Claforan,~~

cefpodoxime: ~~Vantin,~~

cefTAZidime: ~~Fortaz,~~ Tazicef,

cefTRIAXone: ~~Rocephin~~

Action ⬆ ⬇

Inhibits bacterial cell wall synthesis.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Similar to that of second-generation cephalosporins, but activity against staphylococci is less, whereas activity against gram-negative pathogens is greater, even for organisms resistant to first- and second-generation agents.
Notable is increased action against:
- Enterobacter,
- Haemophilus influenzae,
- Escherichia coli,
- Klebsiella pneumoniae,
- Neisseria gonorrhoeae,
- Citrobacter,
- Morganella,
- Proteus,
- Providencia,
- Serratia,
- Moraxella catarrhalis,
- Borrelia burgdorferi.
Some agents have activity against N. meningitidis (cefotaxime, ceftazidime, ceftriaxone).
Some agents have enhanced activity against Pseudomonas aeruginosa (ceftazidime).
Not active against methicillin-resistant staphylococci or enterococci.
Some agents have activity against anaerobes, including Bacteroides fragilis (cefotaxime, ceftriaxone).

Classifications ⬆ ⬇

Therapeutic Classification: anti-infectives

Pharmacologic Classification: third generation cephalosporins

Pharmacokinetics ⬆ ⬇

Absorption: Cefotaxime,ceftazidime, and ceftriaxone are well absorbed after IM administration. Cefixime 40–50% absorbed after oral administration (oral suspension); cefdinir 16–25% absorbed after oral administration. Cefpodoxime proxetil is a prodrug that is converted to its active component in GI tract during absorption (50% absorbed).

Distribution: Widely distributed. CSF penetration better than with first- and second-generation agents.

Protein Binding: Ceftriaxone≥90%.

Metabolism/Excretion: Cefdinir and ceftazidime>85% excreted in urine. Cefpodoxime: 30% excreted in urine. Ceftriaxone and cefotaxime: partly metabolized and partly excreted in the urine. Cefixime: 50% excreted unchanged in urine, ≥10% in bile.

Half-Life: Cefdinir: 1.7 hr; cefixime: 3–4 hr; cefotaxime: 1–1.5 hr; cefpodoxime: 2–3 hr; ceftazidime: 2 hr; ceftriaxone: 6–9 hr (all except ceftriaxone are ↑ in renal impairment).

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
Cefdinir PO	rapid	2–4 hr	12–24 hr
Cefixime PO	rapid	2–6 hr	24 hr
Cefotaxime IM	rapid	0.5 hr	4–12 hr
Cefotaxime IV	rapid	end of infusion	4–12 hr
Cefpodoxime PO	unknown	2–3 hr	12 hr
Ceftazidime IM	rapid	1 hr	6–12 hr
Ceftazidime IV	rapid	end of infusion	6–12 hr
Ceftriaxone IM	rapid	1–2 hr	12–24 hr
Ceftriaxone IV	rapid	end of infusion	12–24 hr

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication around the clock and to finish the medication completely, even if feeling better. Take missed doses as soon as possible unless almost time for next dose; do not double doses. Advise patient that sharing of this medication may be dangerous.
Pedi: Instruct parents or caregivers to use calibrated measuring device with liquid preparations.
Advise patient to report signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools) and allergy.
Instruct patient to notify health care professional if rash, fever, and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.

section name header

Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆