CEFTAROLINE FOSAMIL
Clinical safety rating: safe
Animal studies have demonstrated safety
Ceftaroline fosamil is a prodrug that is converted to the active metabolite ceftaroline. Ceftaroline inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), including PBP2a in MRSA and PBP2x in Streptococcus pneumoniae, thereby preventing cross-linking of peptidoglycan.
| Metabolism | Ceftaroline fosamil is metabolized by plasma phosphatases to active ceftaroline. Ceftaroline is minimally metabolized by the liver and undergoes renal elimination predominantly as unchanged drug. |
| Excretion | Renal excretion of unchanged ceftaroline accounts for approximately 88% of the administered dose. Biliary/fecal elimination is minimal (<6%). |
| Half-life | Terminal elimination half-life is approximately 2.6 hours in patients with normal renal function. This supports twice-daily dosing in most infections. |
| Protein binding | Approximately 20% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.38 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Only administered intravenously; bioavailability is 100% by the IV route. |
| Onset of Action | Intravenous administration: Onset of bactericidal activity occurs within the first hour after infusion initiation. |
| Duration of Action | Duration of bactericidal activity persists for approximately 8–12 hours post-dose, consistent with a q12h dosing interval. |
600 mg IV every 12 hours infused over 1 hour
| Dosage form | POWDER |
| Renal impairment | CrCl 30-50 mL/min: 400 mg IV every 12 hours; CrCl 15-29 mL/min: 300 mg IV every 12 hours; CrCl <15 mL/min or hemodialysis: 200 mg IV every 12 hours |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe impairment (Child-Pugh C) |
| Pediatric use | For ages 2 months to <18 years: 12 mg/kg/dose IV every 8 hours (max 600 mg/dose) infused over 1 hour |
| Geriatric use | No specific dose adjustment based on age alone; adjust based on renal function as per renal adjustment guidelines |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Drugs that prolong the QT interval may have additive effects May cause diarrhea including Clostridium difficile-associated diarrhea.
| Breastfeeding | Ceftaroline is excreted into human breast milk in low concentrations. The milk-to-plasma (M/P) ratio is not established. Based on limited data, it is considered compatible with breastfeeding due to poor oral bioavailability and minimal GI absorption in infants. However, caution is advised, and monitor infant for diarrhea or allergic reactions. |
| Teratogenic Risk | Ceftaroline fosamil is a cephalosporin antibiotic classified as FDA Pregnancy Category B. Animal reproduction studies have not demonstrated fetal harm, but no adequate and well-controlled studies exist in pregnant women. There is no evidence of teratogenicity in first trimester. Risk cannot be ruled out; use only if clearly needed. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Diarrhea |
| Serious Effects |
["Known hypersensitivity to ceftaroline or other cephalosporins","Known hypersensitivity to any component of the formulation"]
| Precautions | ["Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported.","Clostridioides difficile-associated diarrhea (CDAD): May range from mild diarrhea to fatal colitis.","Direct Coombs test seroconversion: May occur and may interfere with cross-matching or antibody testing.","Seizures: Potential for CNS adverse reactions including seizures, especially in patients with renal impairment.","Renal impairment: Dose adjustment required for patients with moderate to severe renal impairment."] |
| Food/Dietary |
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| Fetal Monitoring | No specific fetal monitoring required. Monitor maternal renal function, complete blood count (CBC) with differential, and signs of Clostridioides difficile-associated diarrhea. For prolonged use, assess for superinfection. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility at clinically relevant doses. |
| No specific food interactions. However, avoid alcohol ingestion in cases of liver dysfunction or if other interacting drugs are used. No restrictions on diet. |
| Clinical Pearls | Ceftaroline fosamil, a fifth-generation cephalosporin, has activity against MRSA due to its affinity for PBP2a. It is also active against many Gram-negative pathogens including Enterobacteriaceae but not ESBL-producing strains. Note that it does not cover Pseudomonas aeruginosa. It is used for community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). Like other beta-lactams, it is time-dependent and requires prolonged infusion for optimal pharmacokinetic/pharmacodynamic target attainment (e.g., over 2 hours). It may cause false-positive Coombs test (direct antiglobulin test) and rarely immune-mediated hemolytic anemia. Adjust dose in renal impairment (CrCl ≤50 mL/min). |
| Patient Advice | Take this medication exactly as prescribed; it is given intravenously by a healthcare provider. · Tell your doctor if you have a history of allergies to penicillins, cephalosporins, or other beta-lactams. · Report any signs of allergic reaction such as rash, hives, difficulty breathing, or swelling of the face/throat. · Notify your healthcare provider if you experience severe diarrhea, especially if watery or bloody, as this may indicate Clostridioides difficile infection. · Inform your doctor if you have kidney problems, as dose adjustments may be necessary. · Keep all appointments for blood tests to monitor kidney function and blood cell counts. |