KIMYRSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KIMYRSA (KIMYRSA).
KIMYRSA (dalbavancin) inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of the peptidoglycan precursor, preventing cross-linking.
| Metabolism | Dalbavancin is not significantly metabolized; it undergoes slow hydrolysis to less active metabolites. It is primarily excreted unchanged in urine and feces. Minor involvement of CYP450 enzymes. |
| Excretion | Primarily renal excretion as unchanged drug (approximately 70-80% of the dose). Fecal elimination accounts for about 5-10%. Biliary excretion is minimal. |
| Half-life | Terminal elimination half-life is approximately 6-7 hours in adults with normal renal function. In patients with renal impairment, half-life may be prolonged up to 12-15 hours, requiring dose adjustment. |
| Protein binding | Approximately 80-85% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution ranges from 0.3 to 0.5 L/kg, indicating distribution into extracellular fluid. Higher Vd may be seen in critically ill patients due to increased capillary permeability. |
| Bioavailability | Not applicable; KIMYRSA is only administered intravenously (bioavailability is 100% for IV route). Oral bioavailability is 0%. |
| Onset of Action | Intravenous infusion: Onset of antibacterial effect is rapid, with peak serum concentrations achieved immediately after infusion. Clinical response typically observed within 24-48 hours. |
| Duration of Action | Duration of action is approximately 8-12 hours based on dosing interval. For serious infections, continuous or extended infusion may be used to maintain therapeutic levels. |
15 mg/kg IV every 12 hours for 5-7 days for acute bacterial skin and skin structure infections.
| Dosage form | POWDER |
| Renal impairment | For CrCl 30-89 mL/min: 15 mg/kg IV every 24 hours. For CrCl <30 mL/min: 15 mg/kg IV every 48 hours. CrCl estimated by Cockcroft-Gault. |
| Liver impairment | No specific dose adjustment recommended. Use with caution in severe hepatic impairment (Child-Pugh C) due to limited data. |
| Pediatric use | Not approved for use in pediatric patients <18 years of age. |
| Geriatric use | No dose adjustment based solely on age; adjust dose based on renal function as per renal_adjustment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KIMYRSA (KIMYRSA).
| Breastfeeding | No data on oritavancin in human milk. The M/P ratio is unknown. Oritavancin is highly protein bound (>85%), which may limit excretion into milk, but due to long half-life (13-15 days), potential infant exposure is uncertain. Caution is advised; breastfeeding should be discontinued during therapy and for 4-5 half-lives (up to 60 days) after last dose to minimize infant exposure. |
| Teratogenic Risk | Oritavancin (Kimyrusa) is classified as FDA Pregnancy Category C. Animal studies in rats and rabbits at doses up to 0.5 times the human dose (based on AUC) showed no teratogenicity but maternal toxicity (reduced body weight gain) and fetal effects (delayed ossification, reduced fetal weight) occurred. No adequate human studies exist. Use only if potential benefit justifies risk to fetus. Limited data for first trimester; theoretical risk based on mechanism (cell wall synthesis inhibition) is low but not fully characterized. Avoid in pregnancy unless absolutely necessary. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of hypersensitivity to dalbavancin or other lipoglycopeptides","Known allergy to any component of the formulation"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis","Infusion reactions (e.g., flushing, urticaria, pruritus) – slow infusion rate","Potential for Clostridioides difficile-associated diarrhea","Elevated liver enzymes (monitor LFTs)","Use with caution in patients with renal impairment (CrCl <30 mL/min) as dose adjustment may be required","Not effective against Gram-negative pathogens","Increased risk of bleeding in patients receiving warfarin (prolongation of PT/INR monitoring)"] |
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| Fetal Monitoring | No specific monitoring requirements for oritavancin in pregnancy. Standard monitoring for maternal infusion reactions (e.g., flushing, urticaria, hypotension) during administration. Fetal monitoring for growth and well-being if drug is used in second or third trimester, due to potential maternal toxicity affecting placental blood flow. Assess liver function and renal function as prolonged half-life may require adjustment in severe hepatic impairment. No routine drug level monitoring. |
| Fertility Effects | No human studies on effects on fertility. In animal studies, there were no effects on male or female fertility in rats at doses up to 0.5 times human dose. Mechanism does not suggest direct impact on reproductive organs, but caution due to lack of data. |