Vancomycin (Renal Dosing)

Source: UK SPC (eMC) for Vancomycin 1000 mg powder for concentrate for solution for infusion, section 4.2 (https://www.medicines.org.uk/emc/product/15737/smpc). PRINCIPLE: the INITIAL dose should be based on TOTAL BODY WEIGHT; subsequent dose adjustments should be based on serum concentrations to achieve targeted therapeutic concentrations, and renal function must be taken into consideration for subsequent doses and interval of administration. Where appropriate, vancomycin should be administered in combination with other antibacterial agents. THERAPEUTIC DRUG MONITORING: the frequency of TDM must be individualised, ranging from daily sampling in some haemodynamically unstable patients to at least once weekly in stable responding patients. In patients with normal renal function, measure the serum concentration on the second day of treatment immediately prior to the next dose. In patients on intermittent haemodialysis, levels should usually be obtained before the start of the haemodialysis session. Therapeutic TROUGH (minimum) levels should normally be 10-20 mg/L depending on the site of infection and susceptibility of the pathogen; trough values of 15-20 mg/L are usually recommended by clinical laboratories to better cover susceptible-classified pathogens with MIC 1 mg/L or greater. Model-based methods may be useful in predicting individual dose requirements to reach an adequate AUC, both for calculating a personalised starting dose and for adjustments based on TDM. After ORAL administration, monitoring of serum concentrations should be performed in patients with inflammatory intestinal disorders. PERI-OPERATIVE PROPHYLAXIS OF BACTERIAL ENDOCARDITIS (all age groups): an initial dose of 15 mg/kg prior to induction of anaesthesia; depending on the duration of surgery a second dose may be required. ORAL VANCOMYCIN FOR CLOSTRIDIOIDES DIFFICILE INFECTION (patients 12 years and older): 125 mg every 6 hours for 10 days for the first episode of non-severe CDI; this can be increased to 500 mg every 6 hours for 10 days in severe or complicated disease; maximum daily dose 2 g. For multiple recurrences, consideration may be given to 125 mg four times daily for 10 days followed by either tapering (gradually decreasing to 125 mg per day) or a pulse regimen (125-500 mg/day every 2-3 days for at least 3 weeks). Whenever possible the antibacterial suspected to have caused CDI should be discontinued, and adequate fluid and electrolyte replacement ensured. For oral use the contents of parenteral vials may be used — one 1000 mg vial reconstituted in 30 or 60 mL of water, given to drink or by nasogastric tube. TREATMENT DURATION (tailor to type and severity of infection and clinical response): complicated skin and soft tissue infections, non-necrotising 7 to 14 days, necrotising 4 to 6 weeks (continue until further debridement is not necessary, the patient has clinically improved and has been afebrile for 48 to 72 hours); bone and joint infections 4 to 6 weeks (longer oral suppression may be considered for prosthetic joint infections); community-acquired pneumonia 7 to 14 days; hospital-acquired pneumonia including ventilator-associated pneumonia 7 to 14 days; infective endocarditis 4 to 6 weeks (duration and need for combination therapy based on valve type and organism). ELDERLY: lower maintenance doses may be required due to the age-related reduction in renal function. HEPATIC IMPAIRMENT: no dose adjustment is needed. PREGNANCY: significantly increased doses may be required to achieve therapeutic serum concentrations in pregnant women. OBESE PATIENTS: the initial dose should be individually adapted according to total body weight as in non-obese patients. NEONATES (term, birth to 27 days post-natal age, and preterm, birth to expected date of delivery plus 27 days): the advice of a physician experienced in the management of neonates should be sought; one possible way of dosing given in the SPC is post-menstrual age below 29 weeks — 15 mg/kg every 24 h; 29-35 weeks — 15 mg/kg every 12 h; above 35 weeks — 15 mg/kg every 8 h. Verify all paediatric and neonatal dosing against a children's formulary. SOURCE LIMITATION: eMC section 4.5 was NOT captured in this bundle — the interactions listed below are taken from the US label (openFDA/DailyMed) and must be checked against the UK SPC. Sections 4.4 and 4.8 were truncated at the fetch limit.

Section 4.2: 'Infants and children aged from one month to less than 12 years of age: The recommended dose is 10 to 15 mg/kg body weight every 6 hours.' dosePerKg is left null because the SPC states a RANGE, not a single per-kg value. Patients aged 12 years and older use the adult regimen (15 to 20 mg/kg every 8 to 12 hours, not to exceed 2 g per dose). PAEDIATRIC RENAL ADJUSTMENT: dose adjustment in children aged 1 year and older may be based on eGFR by the revised Schwartz formula — eGFR (mL/min/1.73 m2) = height in cm x 0.413 / serum creatinine in mg/dL, or height in cm x 36.2 / serum creatinine in micromol/L. Orientative paediatric dosing by GFR (mL/min/1.73 m2): 50-30 — 15 mg/kg 12 hourly; 29-10 — 15 mg/kg 24 hourly; below 10 — 10-15 mg/kg, re-dose based on levels; intermittent haemodialysis, peritoneal dialysis or continuous renal replacement therapy — 15 mg/kg, re-dose based on levels. For neonates and infants below 1 year of age, expert advice should be sought as the revised Schwartz formula is not applicable to them. ORAL FOR CLOSTRIDIOIDES DIFFICILE INFECTION (neonates, infants and children under 12 years): 10 mg/kg orally every 6 hours for 10 days, maximum daily dose 2 g. Verify all paediatric dosing against a children's formulary.