Vancomycin Hcl (vancomycin HCl)

Dosage of vancomycin hydrochloride is expressed in terms of vancomycin.

Vancomycin hydrochloride is administered by IV infusion for the treatment of systemic infections.

Vancomycin hydrochloride is administered orally as capsules or solution for the treatment of Clostridioides difficile (formerly known as Clostridium difficile-associated diarrhea or enterocolitis caused by Staphylococcus aureus (including MRSA). If necessary, the parenteral form of vancomycin hydrochloride may be diluted and administered orally by mouth or nasogastric tube for these indications. Orally administered vancomycin is not effective for and should not be used for the treatment of systemic infections.

Vancomycin has been administered rectally+ in the treatment of fulminant CDI in adults.

Safety and efficacy of intrathecal (intralumbar or intraventricular), intracameral, intravitreal, or intraperitoneal administration of vancomycin have not been established.

There is no enhanced messaging for this drug.

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.

Selected Nephrotoxic Agents/Bacitracin

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: Bacitracin may cause renal failure due to glomerular and tubular necrosis. Concurrent administration of other nephrotoxic agents may result in additive renal toxicity.(1-3)

CLINICAL EFFECTS: Concurrent use of bacitracin with other potentially nephrotoxic agents may result in renal toxicity.(1-3)

PREDISPOSING FACTORS: Dehydration and high-dose bacitracin may predispose to adverse renal effects.(1)

PATIENT MANAGEMENT: Health Canada states that bacitracin is contraindicated in patients with renal impairment, including those taking other nephrotoxic drugs.(1) The Canadian and US manufacturers of bacitracin state that concomitant use of bacitracin with other potentially nephrotoxic agents should be avoided.(2,3)

DISCUSSION: Renal impairment is a major toxicity of bacitracin. Cases of nephrotoxicity have been reported when bacitracin was used off-label.(1-3)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

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

Oral Vancomycin/Bile Acid Sequestrants

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

MECHANISM OF ACTION: Bile acid sequestrants bind to vancomycin when the medications are coadministered.(1,2)

CLINICAL EFFECTS: When using both medications concurrently, bile acid sequestrants may bind to oral vancomycin, causing a decrease in its unbound concentration and potentially affecting the antibiotic activity of the medication.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: It has been suggested when using both medications that the course of bile acid sequestrants follow the course of oral vancomycin in order to avoid a reduction in vancomycin concentration by preventing the binding of vancomycin to the bile acid sequestrant.(2,3)

DISCUSSION: One study found when oral vancomycin and cholestyramine were coadministered that the active concentration of vancomycin decreased by as much as 80%.(2) Conversely another study suggests when both medications are used concurrently that vancomycin antibacterial activity is unaffected by cholestyramine binding.(1) Two additional studies looked at the combination of cholestyramine and oral vancomycin for the treatment of C. difficile associated pseudomembranous colitis. One looked at the results from both in vitro and hamster models(4) while the other recorded results from hamster as well as clinical studies.(3) Both of the studies had similar results noting a 10-fold decrease in therapeutically active vancomycin concentration when used in combination with cholestyramine. Both studies also found no clinical benefit from coadministration of the medications versus the use of oral vancomycin alone. Another study found the in vitro combination of cholestyramine and oral vancomycin resulted in substantially decreased vancomycin concentrations potentially hindering its therapeutic activity.(5)

Vancomycin/Gentamicin, Amikacin, Tobramycin

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

MECHANISM OF ACTION: The ototoxic or nephrotoxic effects of gentamicin, amikacin, or tobramycin may be additive with those of vancomycin.

CLINICAL EFFECTS: The concurrent administration of gentamicin, amikacin, or tobramycin with vancomycin may result in additive ototoxic or nephrotoxic effects.(1)

PREDISPOSING FACTORS: Preexisting renal impairment, sepsis, extended duration of aminoglycoside therapy, greater than one aminoglycoside dose per day, or concomitant use of additional nephrotoxic agents such as iodinated contrast media or vancomycin appear to increase the risk for nephrotoxicity and ototoxicity.(1-5). Patients carrying certain variants in the MT-RNR1 gene (m.1555A>G, m.1095T>C, and m.1494C>T) are at increased risk of developing ototoxicity. An additional risk factor includes patients with a maternal relative known to have a clinically relevant MT-RNR1 variant. The risk of ototoxicity can occur at standard recommended doses of aminoglycosides.

PATIENT MANAGEMENT: The Australian manufacturer of gentamicin, amikacin, and tobramycin state that the concurrent use of gentamicin, amikacin, or tobramycin and vancomycin should be avoided.(1,4,5)

DISCUSSION: The Australian and U.K. manufacturers of gentamicin, amikacin, and tobramycin state that since the ototoxic or nephrotoxic effects of gentamicin, amikacin, or tobramycin may be additive, avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic agents including vancomycin.(1,3,4,5)

*Hypersensitivity to vancomycin.

*Commercially available frozen vancomycin hydrochloride injection in 5% dextrose may be contraindicated in patients with known allergy to corn or corn products.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• Severe renal impairment

IV: Local effects (pain and thrombophlebitis); infusion reactions; hypersensitivity reactions.

Oral solution: Nausea, abdominal pain, and hypokalemia.

More Frequent

• Hypokalemia

Less Frequent

• Nephrotoxicity

Rare or Very Rare

• Acute generalized exanthematous pustulosis
• Anaphylaxis
• DRESS syndrome
• Linear immunoglobulin A bullous dermatosis
• Ototoxicity
• Stevens-johnson syndrome
• Toxic epidermal necrolysis
• Vasculitis

More Frequent

• Acute abdominal pain
• Diarrhea
• Dysgeusia
• Fever
• Flatulence
• Nausea
• Peripheral edema
• Urinary tract infection
• Vomiting

Less Frequent

• Fatigue

Rare or Very Rare

• Chills
• Dyspnea
• Eosinophilia
• Hypotension
• Urticaria

No enhanced messaging available.

Safety and efficacy of oral vancomycin have not been established in pediatric patients.

IV vancomycin should be used with caution in premature neonates and young infants because of the renal immaturity of these patients and the potential for increased serum concentrations of the drug. Close monitoring of serum vancomycin concentrations may be warranted in pediatric patients, especially neonates and young infants.

Safety of the chemical components that may leach out of the plastic containers of commercially available frozen vancomycin injections has not been established in children.

There was no evidence of teratogenicity when vancomycin was administered IV to rats in dosages up to 200 mg/kg daily (1180 mg/m2 or equivalent to the recommended maximum human dosage based on mg/m2) or to rabbits in dosages up to 120 mg/kg daily (1320 mg/m2 or 1.1 times the recommended maximum human dosage based on mg/m2). There were no effects on fetal weight or development in rats at the highest dosage tested or in rabbits given 80 mg/kg daily (880 mg/m2 or 0.74 times the maximum recommended human dosage based on mg/m2).

In one study, no sensorineural hearing loss or nephrotoxicity was reported in neonates born to women who received IV vancomycin for severe staphylococcal infections associated with injection drug abuse- during pregnancy. In one infant whose mother received IV vancomycin in the third trimester of pregnancy, conductive hearing loss was reported; however, a causal relationship to vancomycin has not been established. Because the number of pregnant women in this study was limited and vancomycin was only administered during the second and third trimester of pregnancy, it is not known whether the drug can cause fetal harm when administered to pregnant women.

In a prospective study, no major adverse effects were observed in mothers or their newborns when IV vancomycin was administered at the time of delivery. This study included 55 pregnant women with positive group B Streptococcus culture with resistance to clindamycin or unknown sensitivity and a high-risk penicillin allergy. Vancomycin dosage ranged from 1 g every 12 hours to 20 mg/kg (maximum individual dose 2 g) every 8 hours. None of the newborns had sensorineural hearing loss; although renal function of the neonates was not assessed, all neonates were discharged in good condition.

Vancomycin should be used during pregnancy only when clearly needed.

Vancomycin is distributed into milk following IV administration. Systemic absorption of oral vancomycin is very low and it is not known whether the drug distributes into human milk following oral administration. However, IV and oral vancomycin should be used with caution in nursing women. Because of the potential for serious adverse reactions from the drug in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of vancomycin to the woman.

Vancomycin dosage should be adjusted accordingly in geriatric patients; consider the greater frequency of renal impairment in this age group.

In clinical studies of oral vancomycin, 54% of patients were >65 years of age; of these, 40% were >65-75 years of age and 60% were >75 years of age. In these studies, geriatric patients treated with oral vancomycin capsules for diarrhea associated with CDI were more likely to develop nephrotoxicity during or after completion of therapy. Renal function should be monitored during and after treatment with oral vancomycin in all geriatric patients, including those with normal renal function.

Geriatric patients >65 years of age may take longer to respond to oral vancomycin therapy compared with younger patients. Clinicians should be aware of the appropriate duration of oral vancomycin treatment in geriatric patients and therapy should not be prematurely discontinued or prematurely switched to an alternate therapy.

IV vancomycin dosage in geriatric patients should be adjusted based on the degree of renal impairment. Because geriatric patients may have decreasing glomerular filtration with increasing age, increased serum vancomycin concentrations may occur if dosage is not adjusted in these patients.