Covan

Approved Indications:

• Serious or severe infections caused by susceptible strains of Gram-positive bacteria, especially when less toxic alternatives are ineffective or contraindicated, including:
• Methicillin-resistant Staphylococcus aureus (MRSA) infections
• Methicillin-resistant Staphylococcus epidermidis
• Endocarditis (native or prosthetic valve)
• Osteomyelitis
• Septicemia
• Pneumonia
• Skin and soft tissue infections
• Clostridioides difficile–associated diarrhea (CDAD):
• Vancomycin (oral) is indicated for the treatment of C. difficile–induced pseudomembranous colitis.
• Perioperative prophylaxis:
• For patients at high risk for MRSA infection or those with beta-lactam allergy undergoing major surgical procedures (e.g., cardiac or orthopedic surgery).

Clinically Accepted Off-Label Uses:

• Bacterial meningitis (as part of combination therapy, especially for resistant pneumococci)
• Febrile neutropenia in immunocompromised patients
• Ventilator-associated pneumonia (VAP) due to MRSA
• Surgical site infections in high-risk patients

Adults (IV):

• Standard serious infections: 15–20 mg/kg every 8–12 hours
• MRSA infections or pneumonia: Target trough 15–20 mcg/mL
• Duration: Typically 7–14 days depending on severity/site

Adults (Oral):

• C. difficile infection:
• Initial episode: 125 mg orally 4 times daily for 10 days
• Severe/fulminant cases: 500 mg 4 times daily ± rectal vancomycin

Pediatrics (IV):

• 10–15 mg/kg every 6–12 hours; adjust per trough levels

Pediatrics (Oral for CDI):

• 10 mg/kg/dose (max 125 mg/dose) every 6 hours for 10 days

Renal Impairment (IV):

• Dose adjustment required based on creatinine clearance (CrCl)
• Use trough levels for monitoring (goal 10–20 mcg/mL)

Administration:

• IV Infusion: Administer over at least 60 minutes (≤10 mg/min) to reduce risk of "Red man syndrome"
• Oral Route: Not absorbed systemically—used only for GI infections like C. difficile

Vancomycin is a glycopeptide antibiotic that inhibits bacterial cell wall synthesis by binding firmly to the D-alanyl-D-alanine terminus of cell wall precursor units. This prevents polymerization of peptidoglycan chains and inhibits transglycosylation, leading to weakened cell wall structure and bacterial cell lysis. It is bactericidal against most Gram-positive organisms and is especially effective against multidrug-resistant strains such as MRSA and C. difficile (when given orally).

• Absorption: Poor oral absorption; systemic absorption negligible (oral route is for GI infections only).
• Distribution: Widely distributed; good penetration into pleural, pericardial, ascitic fluids; variable CNS penetration unless meninges are inflamed.
• Protein Binding: ~55%
• Metabolism: Not extensively metabolized
• Half-life:
• Normal renal function: 4–6 hours
• End-stage renal disease: up to 7 days
• Excretion: Primarily via kidneys (glomerular filtration); ~80–90% excreted unchanged in urine

• Pregnancy: Category B (based on FDA classification). No evidence of teratogenicity in animal studies. Use only if clearly needed.
• Lactation: Vancomycin is excreted into breast milk in small amounts. Caution is advised. Monitor the breastfed infant for gastrointestinal disturbances or oral thrush, though systemic effects are unlikely.

·         Primary Class: Glycopeptide antibiotic

·         Subclass: Tricyclic glycopeptide

·         Generation: First-generation glycopeptide

• Known hypersensitivity to vancomycin or any of its components
• Prior anaphylactic reaction to vancomycin
• Avoid oral form in systemic infections (ineffective systemically)

• Red Man Syndrome: Rapid IV infusion may cause histamine-mediated flushing, rash, hypotension. Infuse slowly over ≥60 minutes.
• Nephrotoxicity: Increased risk when used with aminoglycosides or in high trough levels
• Ototoxicity: Rare; associated with high doses or prolonged therapy, especially with other ototoxic drugs
• Superinfection: Long-term use may result in overgrowth of non-susceptible organisms, including fungi
• Therapeutic Drug Monitoring (TDM): Recommended for IV vancomycin; trough levels guide dosing adjustments
• Pseudomembranous colitis risk: While oral vancomycin treats C. difficile, IV form is ineffective for colitis
• Renal function monitoring: Required in elderly and renally impaired patients

Common:

• Infusion-related reactions (Red Man Syndrome)
• Rash
• Phlebitis at IV site
• Fever
• Nausea

Less Common but Serious:

• Nephrotoxicity (elevated creatinine, renal impairment)
• Ototoxicity (hearing loss, tinnitus)
• Neutropenia, thrombocytopenia
• Eosinophilia
• Anaphylaxis or severe allergic reactions

Rare:

• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Interstitial nephritis
• Stevens-Johnson Syndrome

• Aminoglycosides (e.g., gentamicin): ↑ Risk of nephrotoxicity and ototoxicity
• Loop diuretics (e.g., furosemide): ↑ Ototoxic potential
• Cisplatin: Enhanced nephrotoxicity
• Anesthesia (e.g., muscle relaxants): May potentiate neuromuscular blockade
• Cholestyramine: May bind oral vancomycin in GI tract and reduce efficacy in CDI

Enzyme systems: Not significantly metabolized by CYP450; minimal enzyme interaction

• IDSA (Infectious Diseases Society of America) CDI Guidelines:
• Oral vancomycin now recommended as first-line treatment for initial and recurrent C. difficile infection over metronidazole
• 2020 AUC/MIC-Based Monitoring Update:
• IDSA recommends AUC:MIC ratio (target 400–600) rather than relying solely on trough levels in serious MRSA infections
• Updated surgical prophylaxis guidelines recommend vancomycin only in patients with MRSA risk or beta-lactam allergy

• IV Powder for Injection:
• Store between 20°C and 25°C (68°F–77°F)
• Protect from moisture and light
• Reconstituted solutions are stable for 14 days under refrigeration (2°C–8°C)
• Oral Solution (compounded):
• Store in refrigerator (2°C–8°C)
• Stable for up to 14 days; shake well before use
• Ready-to-use IV bags:
• Do not freeze
• Protect from light
• Use within specified time as per manufacturer's labeling