KHINDIVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KHINDIVI (KHINDIVI).
KHINDIVI (ceftaroline fosamil) is a cephalosporin antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), including PBP2a in methicillin-resistant Staphylococcus aureus (MRSA).
| Metabolism | Ceftaroline fosamil is hydrolyzed by plasma phosphatases to active ceftaroline; it undergoes minimal hepatic metabolism. |
| Excretion | Renal: 60% unchanged; biliary/fecal: 30% as metabolites; 10% other. |
| Half-life | Terminal half-life: 12 hours (range 10-14 hours). Prolonged in renal impairment (up to 24 hours). |
| Protein binding | 95% bound to albumin. |
| Volume of Distribution | 0.5 L/kg (total body water). Indicates extensive tissue distribution. |
| Bioavailability | Oral: 80%; Intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours; Intravenous: 5-15 minutes. |
| Duration of Action | Oral: 12-24 hours; Intravenous: 6-12 hours, depending on dose and renal function. |
1 mg subcutaneously once daily in combination with a sulfonylurea or insulin for type 2 diabetes.
| Dosage form | SOLUTION |
| Renal impairment | eGFR ≥60 mL/min: no adjustment; eGFR 30–59 mL/min: no adjustment; eGFR 15–29 mL/min: no data; eGFR <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B or C: not recommended due to lack of data. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No dose adjustment recommended based on age; monitor renal function due to increased risk of hypoglycemia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KHINDIVI (KHINDIVI).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. In animal studies, fostamatinib and its active metabolite were present in rat milk. Due to potential for serious adverse reactions, advise women not to breastfeed during treatment and for at least 1 month after last dose. |
| Teratogenic Risk | Khindivi (fostamatinib) is an inhibitor of spleen tyrosine kinase (SYK). In animal studies, fetal malformations and embryofetal toxicity occurred at maternal exposures below the human clinical exposure. There are no adequate and well-controlled studies in pregnant women. Use is contraindicated in pregnancy. First trimester: High risk of teratogenicity based on mechanism and animal data. Second/third trimester: Risk of fetal harm; consider discontinuation if pregnancy occurs. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["Known hypersensitivity to ceftaroline or other cephalosporins","History of immediate-type hypersensitivity reaction to penicillins or other beta-lactams"]
| Precautions | ["Hypersensitivity reactions, including anaphylaxis","Clostridioides difficile-associated diarrhea (CDAD)","Direct Coombs test seroconversion (potential for hemolytic anemia)","Seizures (in patients with renal impairment)","Suprainfection, including Clostridioides difficile overgrowth"] |
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| Fetal Monitoring | Pregnancy testing prior to initiation; confirm non-pregnant status. During treatment, monitor for pregnancy if sexually active. If pregnancy occurs, immediate discontinuation recommended. Monitor for hepatic transaminase elevations (ALT/AST) and hypertension, as these are known adverse effects that may complicate pregnancy. |
| Fertility Effects | Based on animal studies, fostamatinib may impair fertility in females (ovarian effects) and males (testicular degeneration, decreased sperm motility). Human data insufficient to characterize effect on fertility. |