Ceftaroline Fosamil (ceftaroline fosamil acetate)

Ceftaroline fosamil is commercially available as ceftaroline fosamil monoacetate monohydrate; dosage is expressed in terms of anhydrous ceftaroline fosamil.

Dosage of ceftaroline fosamil should be selected with caution in geriatric patients. Dosage adjustments are not required based on age, but may be required based on age-related changes in renal function. (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)

Dosage of ceftaroline fosamil must be modified according to the degree of renal impairment in adults with creatinine clearances of 50 mL/minute or less, including those undergoing hemodialysis. (See Table 1.)

Table 1. Ceftaroline Fosamil Dosage for Adults with Renal Impairment

Estimated Creatinine Clearance Recommended Dosage (mL/minute) 31-50 400 mg every 12 hours 15-30 300 mg every 12 hours <15 or receiving hemodialysis 200 mg every 12 hours; on hemodialysis days, give dose after hemodialysis

Dosage adjustments are not necessary if ceftaroline fosamil is used in pediatric patients with creatinine clearances greater than 50 mL/minute per 1.73 m2. Data are insufficient to make dosage recommendations for pediatric patients with creatinine clearances less than 50 mL/minute per 1.73 m2.

Pharmacokinetics of ceftaroline fosamil have not been studied in patients with impaired hepatic function, but hepatic impairment is not expected to have a clinically important effect on systemic clearance of the drug.

Ceftaroline fosamil is administered by IV infusion.

Ceftaroline fosamil solutions should not be admixed with or added to solutions containing other drugs.

No formal drug interaction studies have been performed to date using ceftaroline fosamil. Interactions are unlikely between ceftaroline fosamil and drugs that are cytochrome P-450 (CYP) substrates, inhibitors, or inducers or drugs that undergo active renal secretion or alter renal blood flow.

In vitro, ceftaroline does not inhibit CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4 and does not induce CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 3A4/5. Therefore, pharmacokinetic interactions with drugs metabolized by these isoenzymes are unlikely.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Slt Cephalosporins/Slt Anticoagulants (Vit K Antagonists)

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown, but may involve a combination of cephalosporin induced platelet inhibition and alteration of gut flora.

CLINICAL EFFECTS: Concurrent use of some cephalosporins may increase the hypoprothrombinemic effect of the anticoagulant with possible bleeding.

PREDISPOSING FACTORS: High doses, hepatic and/or renal impairment, and poor nutrition may increase the risk of bleeding. The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: Monitor prothrombin activity and adjust the anticoagulant dosage accordingly. Consider using an alternative antibiotic. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: Although the majority of cephalosporins that have been documented to interact with anticoagulants have a NMTT side chain, there are reports of interactions with cefazolin, cefoxitin, ceftaroline, and ceftriaxone as well. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 11 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and antimicrobials (OR=1.63; 95% CI 1.45-1.83). Increased bleeding risk was also seen in subgroup analyses with cephalosporins (OR=1.50; 95% CI 1.21-1.86).

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Clostridioides difficile infection
• Hemolytic anemia

• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Lower seizure threshold
• Myoclonus
• Seizure disorder

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Less Frequent

• Abnormal hepatic function tests
• Hypokalemia
• Increased alanine transaminase
• Increased aspartate transaminase

Rare or Very Rare

• Agranulocytosis
• Anaphylaxis
• Bradycardia
• Clostridioides difficile infection
• Encephalopathy
• Eosinophilic pneumonia
• Hemolytic anemia
• Hepatitis
• Hyperkalemia
• Renal failure
• Seizure disorder
• Thrombocytopenic disorder

More Frequent

• Diarrhea
• Nausea
• Skin rash

Less Frequent

• Constipation
• Fever
• Headache disorder
• Phlebitis after infusion
• Pruritus of skin
• Vomiting

Rare or Very Rare

• Acute abdominal pain
• Anemia
• Dizziness
• Eosinophilia
• Hyperglycemia
• Myoclonus
• Neutropenic disorder
• Palpitations
• Urticaria

No enhanced messaging available.

No enhanced messaging available.

Adequate data are not available regarding use of ceftaroline fosamil in pregnant women.

Animal studies in rats using ceftaroline fosamil dosages up to 4 times the maximum recommended human dosage (MRHD) or in rabbits using dosages up to approximately equal to the MRHD have not revealed evidence of fetal harm.

It is not known whether ceftaroline is distributed into human milk; possible effects of the drug on a breast-fed infant or on milk production are unknown.

Benefits of breast-feeding and the importance of ceftaroline fosamil to the woman should be considered along with the potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

No enhanced messaging available.