Vancomycin Rompharm lyophilisate for solution for infusion 1000 mg bottle No. 1

Instructions Vancomycin Rompharm lyophilisate for solution for infusion 1000 mg bottle No. 1

Composition

active ingredient: vancomycin hydrochloride;

1 vial contains 1000 mg of vancomycin hydrochloride, equivalent to 1,000,000 IU of vancomycin;

excipients: none.

Dosage form

Lyophilisate for concentrate for infusions.

Main physicochemical properties: sterile powder from white to light brown.

Pharmacotherapeutic group

Glycopeptide antibacterial agents

ATX code:

J01XA01 — vancomycin for intravenous use,

A07AA09 — vancomycin for oral use.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Vancomycin is a tricyclic glycopeptide antibiotic that inhibits cell wall synthesis in susceptible bacteria by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursors. The drug has a slow bactericidal effect on dividing microorganisms. In addition, it disrupts the permeability of the bacterial cell membrane and RNA synthesis.

Pharmacokinetic (PK) / pharmacodynamic (PD) relationship

Vancomycin exhibits concentration-independent activity, with the area under the concentration curve (AUC) divided by the minimum inhibitory concentration (MIC) for the target organism being the primary predictor of efficacy. Based on in vitro animal data and limited human data, an AUC/MIC ratio of 400 has been established as the target PK/PD for vancomycin to achieve clinical efficacy. To achieve this goal, high-range dosing and high serum concentrations (15–20 mg/L) are required at MICs ≥ 1.0 mg/L (see Dosage and Administration).

Mechanism of resistance

Acquired resistance to glycopeptides is most common in enterococci and is based on the acquisition of various van gene complexes that modify D-alanyl-D-alanine targets to D-alanyl-D-lactate or D-alanyl-D-serine, which bind vancomycin poorly. Some countries have seen an increase in resistance, especially in enterococci; multidrug-resistant strains of Enterococcus faecium are of particular concern.

Van genes are rare in Staphylococcus aureus, where changes in cell wall structure result in "intermediate" susceptibility, which is often heterogeneous. Strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin have also been reported. The mechanism of reduced susceptibility or resistance to vancomycin in staphylococci is not fully understood. Multiple genetic elements and numerous mutations are required.

Cross-resistance between vancomycin and other classes of antibiotics is absent. Cross-resistance with other glycopeptide antibiotics, such as teicoplanin, still occurs. Secondary development of resistance during therapy is rare.

Synergy

The combination of vancomycin with an aminoglycoside antibiotic has a synergistic effect against many strains of Staphylococcus aureus, non-enterococcal group D streptococci, enterococci, and viridans streptococci. The combination of vancomycin with a cephalosporin has a synergistic effect against some strains of Staphylococcus epidermidis that are resistant to oxacillin, and the combination of vancomycin with rifampicin has a synergistic effect against Staphylococcus epidermidis and a partial synergistic effect against some strains of Staphylococcus aureus. Since vancomycin in combination with a cephalosporin may also have an antagonistic effect against some strains of Staphylococcus epidermidis and in combination with rifampicin against some strains of Staphylococcus aureus, it is advisable to conduct preliminary testing for synergy.

Bacterial culture samples should be obtained to isolate and identify the pathogens and determine their susceptibility to vancomycin.

Breakpoints in susceptibility testing

Vancomycin is active against gram-positive bacteria such as staphylococci, streptococci, enterococci, pneumococci, and clostridia. Gram-negative bacteria are resistant to vancomycin.

The prevalence of acquired resistance to individual species may vary geographically and over time, and local information on resistance is therefore desirable, particularly in the treatment of severe infections. Expert advice should be sought if the local prevalence of resistance is such that the usefulness of the drug in at least some types of infections is questionable. This information only provides a rough indication of the susceptibility of organisms to vancomycin.

Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

1S. aureus with vancomycin MIC values of 2 mg/L are at the border of the wild-type distribution, and a deterioration in clinical response may be observed.

Pharmacokinetics

Absorption

Vancomycin is administered intravenously to treat systemic infections.

In patients with normal renal function, intravenous infusion of multiple doses of 1 g vancomycin (15 mg/kg) over 60 minutes produces approximate mean plasma concentrations of 50–60 mg/L, 20–25 mg/L, and 5–10 mg/L immediately, 2 hours, and 11 hours after completion of the infusion, respectively. Plasma levels obtained after multiple doses are similar to those achieved after a single dose.

Vancomycin is not normally absorbed into the bloodstream after oral administration. However, absorption may occur after oral administration in patients with (pseudomembranous) colitis. This may lead to accumulation of vancomycin in patients with concomitant renal insufficiency.

Distribution

The volume of distribution is approximately 60 L/1.73 m2 of body surface area. At serum vancomycin concentrations of 10 mg/L to 100 mg/L, plasma protein binding is approximately 30–55% (measured by ultrafiltration).

Vancomycin readily diffuses across the placenta and is distributed in cord blood. In non-inflamed meninges, vancomycin only slightly crosses the blood-brain barrier.

Biotransformation

Vancomycin metabolism is very low. After parenteral administration, the drug is almost completely excreted as microbiologically active substance (approximately 75–90% within 24 hours) by the kidneys by glomerular filtration.

Elimination

The elimination half-life of vancomycin is 4–6 hours in patients with normal renal function and 2.2–3 hours in children. Plasma clearance is approximately 0.058 L/kg/h and renal clearance is approximately 0.048 L/kg/h. During the first 24 hours, approximately 80% of the administered vancomycin dose is excreted in the urine by glomerular filtration. Impaired renal function delays the elimination of vancomycin. In patients with anephric disease, the mean elimination half-life is 7.5 days. Due to the ototoxicity of vancomycin, monitoring of plasma concentrations during therapy is indicated in such cases.

Excretion with bile is insignificant (less than 5% of the dose).

Although vancomycin is not effectively removed by hemodialysis or peritoneal dialysis, there are reports of increased vancomycin clearance with hemoperfusion and hemofiltration.

After oral administration, only a fraction of the administered dose is recovered in the urine. In contrast, high concentrations of vancomycin are found in the feces (> 3100 mg/kg at doses of 2 g/day).

Linearity/nonlinearity

Vancomycin concentrations generally increase proportionally with increasing dose. Plasma concentrations after multiple doses are similar to those after a single dose.

Certain patient groups

Patients with renal impairment. Vancomycin is primarily eliminated by glomerular filtration. In patients with renal impairment, the terminal half-life of vancomycin is prolonged and the total clearance is reduced. Subsequently, the optimal dose should be calculated according to the dosing recommendations given in the section “Method of administration and dosage”.

Patients with hepatic impairment: The pharmacokinetics of vancomycin are not altered in patients with hepatic impairment.

Pregnant women: Significantly higher doses may be required to achieve therapeutic serum concentrations in pregnant women (see section “Use during pregnancy and lactation”).

Overweight patients. The disposition of vancomycin may be altered in overweight patients due to increased volume of distribution, renal clearance, and possible changes in plasma protein binding. In this subpopulation, serum vancomycin concentrations were higher than expected in healthy adult males (see section 4.4).

Children. The pharmacokinetics of vancomycin show wide intersubject variability in preterm and term neonates. In neonates, after intravenous administration, the volume of distribution of vancomycin ranges from 0.38 to 0.97 L/kg, similar to values in adults, while clearance ranges from 0.63 to 1.4 mL/kg/min. The elimination half-life ranges from 3.5 to 10 hours and is longer than in adults, reflecting the usual lower clearance values in neonates.

In infants and older children, the volume of distribution ranges from 0.26 to 1.05 L/kg and the clearance is 0.33 to 1.87 mL/kg/min.

Indication

Vancomycin Rompharm is indicated for all age groups for the treatment of the following infections (see also sections “Method of administration and dosage”, “Special instructions for use” and “Pharmacological properties”):

- complicated skin and soft tissue infections;

- bone and joint infections;

- community-acquired pneumonia;

- hospital-acquired pneumonia, including pneumonia associated with mechanical ventilation;

- infective endocarditis.

Vancomycin Rompharm is also indicated for all age groups for perioperative antibacterial prophylaxis in cases of high risk of bacterial endocarditis during major surgical procedures.

Oral administration

Vancomycin Rompharm is indicated for all age groups for the treatment of Clostridioides difficile infections (see also sections “Method of administration and dosage”, “Special instructions for use” and “Pharmacological properties”).

In addition, official recommendations on the appropriate use of antibacterial agents should be considered.

Contraindication

Hypersensitivity to vancomycin.

Vancomycin should not be administered intramuscularly due to the risk of necrosis at the injection site.

Interaction with other medicinal products and other types of interactions

Concomitant use of vancomycin and anesthetics has been associated with erythema, histamine-like hyperemia, and anaphylactoid reactions (see section 4.4).

An increased incidence of infusion-related adverse reactions has been reported with concomitant use of anesthetics. Infusion-related adverse reactions may be minimized by administering vancomycin as a 60-minute infusion prior to the administration of anesthetics. When administered during anesthesia, the dose should be diluted to 5 mg/mL or less and administered slowly with careful cardiac monitoring. Repositioning of the patient should be delayed until the infusion is complete.

Concomitant or sequential systemic or topical use of other potentially ototoxic or nephrotoxic drugs such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, cisplatin, piperacillin/tazobactam, loop diuretics and NSAIDs may increase the toxicity of vancomycin. Caution and appropriate monitoring are required in such cases (see section 4.4).

The combination of vancomycin with an aminoglycoside antibiotic has a synergistic effect against many strains of Staphylococcus aureus, non-enterococcal D-streptococci, enterococci, and Viridans group streptococci.

The combination of vancomycin with rifampicin has a synergistic effect against Staphylococcus epidermidis.

Oral use: Consideration should be given to discontinuing proton pump inhibitors and motility agents in accordance with local guidelines for Clostridioides difficile infection.

Application features

Hypersensitivity reactions

Serious and sometimes fatal hypersensitivity reactions are possible (see sections 4.3 and 4.8). If hypersensitivity reactions occur, treatment with vancomycin should be discontinued immediately and appropriate emergency measures should be taken.

In patients receiving vancomycin for a long time or concomitantly with other drugs that can cause neutropenia or agranulocytosis, the white blood cell count should be monitored regularly. Periodic blood, urine, liver and kidney function tests should be performed in all patients receiving vancomycin.

Vancomycin should be used with caution in patients with allergic reactions to teicoplanin, as cross-hypersensitivity, including fatal anaphylactic shock, may develop.

Spectrum of antibacterial action

The antibacterial spectrum of vancomycin is limited to gram-positive organisms. Vancomycin should not be used as a single agent for the treatment of certain types of infections unless the pathogen is identified and known to be susceptible to vancomycin, or there is a high probability that the likely pathogen is susceptible to vancomycin.

Empirical use of vancomycin should take into account the bacterial spectrum of activity, safety profile, and suitability of standard antibacterial therapy for the treatment of the individual patient.

Ototoxicity

Ototoxicity, both transient and irreversible (see section 4.8), has been reported in patients with pre-existing deafness who have received excessive intravenous doses or who have been treated concomitantly with another ototoxic agent such as an aminoglycoside. Vancomycin should also be avoided in patients with pre-existing hearing loss. Tinnitus may precede hearing loss. Experience with other antibiotics suggests that deafness may progress despite discontinuation of treatment. To reduce the risk of ototoxicity, vancomycin blood levels should be measured periodically and hearing function should be monitored periodically.

Elderly people are particularly susceptible to hearing damage. Monitoring of vestibular and auditory function in elderly people should be carried out during and after treatment. Concomitant or sequential use of other ototoxic substances should be avoided.

Rapid bolus administration (i.e., over a few minutes) may be associated with increased hypotension (including shock and, rarely, cardiac arrest), histamine-like reactions, and maculopapular rash. Rapid intravenous administration of vancomycin hydrochloride for injection may also be associated with a "vancomycin infusion reaction," which manifests as pruritus and erythema affecting the face, neck, and upper trunk ("red man syndrome" or "red neck syndrome"). Vancomycin should be administered slowly in a dilute solution (2.5 to 5.0 mg/mL) at a rate of no more than 10 mg/min for at least 60 minutes to avoid rapid infusion-related reactions. Discontinuation of the infusion usually results in rapid resolution of these reactions.

Adverse drug reactions are dependent on both the concentration and rate of vancomycin administration. However, infusion-related adverse reactions can occur at any rate or concentration.

The incidence of infusion-related reactions (hypotension, flushing, erythema, urticaria and pruritus) is increased by concomitant use of anaesthetics (see section 4.5). This risk can be reduced by administering vancomycin by infusion for at least 60 minutes before induction of anaesthesia.

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported with vancomycin therapy (see section 4.8). The majority of these reactions occurred within a few days to eight weeks of starting vancomycin therapy.

Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If symptoms suggestive of these reactions occur, vancomycin should be discontinued immediately and alternative treatment considered. If a patient develops TSR while receiving vancomycin, vancomycin should not be restarted under any circumstances.

Injection site reactions

Pain and thrombophlebitis may occur in many patients receiving intravenous vancomycin and are sometimes severe. The incidence and severity of thrombophlebitis can be minimized by administering the drug slowly as a diluted solution (see section 4.2) and by regularly changing the infusion site.

The efficacy and safety of vancomycin when administered by the intrathecal, intralumbar, and intraventricular routes have not been established.

Nephrotoxicity

Vancomycin should be used with caution in patients with renal insufficiency, including anuria, as the likelihood of toxic effects is significantly higher with prolonged presence of high blood concentrations. The risk of toxicity increases with high blood concentrations or prolonged treatment.

Monitoring of vancomycin blood levels is indicated during high-dose therapy and long-term use, especially in patients with impaired renal function or hearing impairment, and in the case of concomitant use of nephrotoxic or ototoxic substances, respectively (see sections 4.2 and 4.5).

Vision impairment

Vancomycin is not approved for intracameral or intravitreal use, including the prophylaxis of endophthalmitis.

Hemorrhagic occlusive retinal vasculitis, including irreversible vision loss, has been observed in isolated cases following intracameral or intravitreal administration of vancomycin during or after cataract surgery.

Clostridioides difficile-associated diarrhea (CDAD)

Clostridioides difficile-associated diarrhea has been reported with nearly all antibacterial agents, including vancomycin. This diarrhea can range in severity from mild diarrhea to fatal colitis. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and may require colectomy. The possibility of CDAD should be considered in all patients who develop diarrhea after antibiotic use. Because CDAD can occur within two months of antibiotic administration, the patient's medical history should be carefully reviewed.

If CDAD is suspected or confirmed, ongoing use of antibiotics not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte monitoring, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be considered as appropriate for the clinical presentation of the patient.

Children

Vancomycin should be used with particular caution in premature neonates and young infants (1 month (28 days) to 23 months of age) due to the immaturity of their kidneys and the potential for increased serum vancomycin concentrations. In such children, vancomycin blood concentrations should be carefully monitored.

Concomitant use of vancomycin and anaesthetics has been associated with erythema and histamine-like hyperaemia in children. Similarly, concomitant use with nephrotoxic agents such as aminoglycoside antibiotics, NSAIDs (e.g. ibuprofen for closure of patent ductus arteriosus) or amphotericin B is associated with an increased risk of nephrotoxicity (see section 4.5), and therefore more frequent monitoring of vancomycin serum levels and renal function is necessary.

Elderly people

The natural decline in glomerular filtration rate with age may lead to increased serum vancomycin concentrations if the dose is not adjusted (see section 4.2).

Interaction with anesthetics

Vancomycin may potentiate myocardial depression caused by the anesthetic. During anesthesia, doses should be well diluted and administered slowly with careful cardiac monitoring. Positioning should be delayed until the infusion is complete (see section 4.5).

Pseudomembranous enterocolitis

In case of severe, prolonged diarrhoea, the possibility of pseudomembranous enterocolitis, which may be life-threatening, should be considered (see section 4.8). Antidiarrhoeal medicinal products should not be given.

Superinfection

Prolonged use of vancomycin may result in overgrowth of nonsusceptible organisms. The patient should be closely monitored. If superinfection occurs during therapy, appropriate measures should be taken.

Oral administration

Intravenous vancomycin is ineffective for the treatment of Clostridioides difficile infection. For this indication, vancomycin should be administered orally.

Testing for Clostridioides difficile colonization or toxin is not recommended in children younger than 1 year of age because of the high rate of asymptomatic colonization, except in cases of severe diarrhea in infants with risk factors for stasis, such as Hirschsprung's disease, surgical anal atresia, or other severe motility disorders. An alternative etiology should always be sought and Clostridioides difficile enterocolitis should be confirmed.

Possibility of systemic absorption

Absorption may be increased in patients with inflammatory bowel disease or pseudomembranous colitis caused by Clostridioides difficile. These patients are at increased risk of adverse reactions, especially if there is concomitant renal insufficiency. The more impaired renal function, the greater the risk of adverse reactions associated with parenteral administration of vancomycin. Serum vancomycin concentrations should be monitored in patients with inflammatory bowel disease.

Nephrotoxicity

When treating patients with impaired renal function or patients receiving concomitant therapy with aminoglycosides or other nephrotoxic drugs, renal function should be monitored consistently.

Ototoxicity

Serial auditory function tests may be useful in minimizing the risk of ototoxicity in patients with primary hearing loss or those receiving concomitant therapy with an ototoxic agent such as an aminoglycoside.

Interaction with antimotility agents and proton pump inhibitors

Motility depressants should be avoided and proton pump inhibitors should be reconsidered.

Development of drug-resistant bacteria

Oral vancomycin administration increases the likelihood of vancomycin-resistant enterococci developing in the gastrointestinal tract. Therefore, caution is recommended when using oral vancomycin.

Use during pregnancy or breastfeeding

Pregnancy

Animal teratology studies in which rats and rabbits were given doses of vancomycin 5 and 3 times the human dose, respectively, revealed no evidence of harm to the fetus.

A controlled clinical trial evaluated the potential ototoxic and nephrotoxic effects of vancomycin hydrochloride on infants when the drug was administered to pregnant women for serious staphylococcal infections. Vancomycin hydrochloride was detected in cord blood. No sensorineural hearing loss or nephrotoxicity related to vancomycin was observed. One infant whose mother received vancomycin in the third trimester developed conductive hearing loss that was not related to vancomycin. Because vancomycin was administered only in the second and third trimesters, it is unknown whether it harms the fetus. Vancomycin should be administered during pregnancy only when clearly needed, and blood levels should be carefully monitored to minimize the risk of fetal toxicity. However, it has been reported that pregnant patients may require significantly higher doses of vancomycin to achieve therapeutic serum concentrations.

Vancomycin hydrochloride is excreted in human milk. Caution should be exercised when vancomycin is administered to a nursing woman. It is believed that the amount of vancomycin that may enter the infant through breast milk is negligible.

Ability to influence reaction speed when driving vehicles or other mechanisms

During the period of use of the drug, the ability to concentrate may decrease, which should be taken into account when driving a car or performing work that requires increased attention.

Method of administration and doses

If necessary, vancomycin should be used in combination with other antibacterial agents.

Intravenous administration

The initial dose should be determined according to total body weight. Subsequent dose adjustments should be based on serum concentrations to achieve target therapeutic concentrations. Renal function should be taken into account when determining subsequent doses and dosing intervals.

Patients aged 12 years and over

The recommended dose is 15–20 mg/kg body weight every 8–12 hours (not to exceed 2 g per dose).

For critically ill patients, a loading dose of 25–30 mg/kg body weight may be used to promote rapid achievement of the target vancomycin trough serum concentration.

Children aged 1 month to 12 years

The recommended dose is 10 to 15 mg/kg body weight every 6 hours (see section "Special instructions").

Full-term newborns (from birth to 27 days) and preterm newborns (from birth to the expected date of delivery plus 27 days)

For the establishment of a dosage regimen for neonates, advice should be sought from a physician experienced in the treatment of neonates. An example of vancomycin dosage for neonates is given in the table below (see also section “Special instructions”).

PMA — postmenstrual age [the time elapsed from the first day of the last menstrual period to birth (gestational age) plus the time elapsed after birth (postpartum age)].

Perioperative prophylaxis of bacterial endocarditis in all age groups

The recommended dose is an initial dose of 15 mg/kg before induction of anesthesia. Depending on the duration of the surgery, a second dose of vancomycin may be required.

Duration of treatment

The recommended duration of treatment is given in the table below. In each case, the duration of treatment should be adapted to the type and severity of the infection and the individual clinical response.

*Continue until no further wound care is required and the patient is clinically improving. Discontinue if the patient has a fever for 48–72 hours.

** For prosthetic joint infections, longer courses of oral suppressive therapy should be considered.

***The duration and need for combination therapy depends on the type of heart valve and the pathogen.

Special patient groups

Elderly people

Lower maintenance doses may be required due to age-related decline in renal function.

Kidney dysfunction

For adults and children with renal insufficiency, dosing may need to be based on serum vancomycin levels, especially in patients with severe renal insufficiency or those undergoing renal replacement therapy (RRT), due to the many different factors that can affect vancomycin levels.

In patients with mild or moderate renal impairment, the initial dose should not be reduced. In patients with severe renal impairment, it is preferable to prolong the dosing interval rather than to prescribe lower daily doses.

The appropriateness of the concomitant use of medicinal products that may reduce the clearance of vancomycin and/or enhance its undesirable effects should be carefully considered (see section "Special warnings and precautions for use").

Vancomycin is poorly removed by intermittent hemodialysis. However, the use of high-flux membranes and continuous renal replacement therapy (CRRT) increases vancomycin clearance and usually requires dose adjustment (usually after an intermittent hemodialysis session).

Adults: Dose adjustments for adult patients may be based on estimated glomerular filtration rate (GFR) using the following formula:

Men: [weight (kg) × (140 – age (years))] / (72 × serum creatinine (mg/dL))

The usual starting dose for adults is 15 to 20 mg/kg, which may be administered every 24 hours in patients with creatinine clearance between 20 and 49 ml/min. In patients with severe renal impairment (creatinine clearance below 20 ml/min) or in patients receiving renal replacement therapy, the dosage and number of subsequent doses depend largely on the method of administration and should be based on trough serum vancomycin levels and residual renal function (see section 4.4). Depending on the clinical situation, the next dose may be withheld until vancomycin levels are available.

For critically ill patients with renal insufficiency, the initial loading dose (25–30 mg/kg) should not be reduced.

Children: Dose adjustment for children aged 1 year and older may be based on the estimated glomerular filtration rate (GFR) using the Schwartz formula:

GFR (ml/min/1.73 m2) = (height (cm) × 0.413) / serum creatinine (mg/dl)

GFR (ml/min/1.73 m2) = (height (cm) × 36.2) / serum creatinine (μmol/L)

When treating children under 1 year of age, expert advice should be sought, as the Schwartz formula does not apply to them.

The table below provides dosing recommendations for children, which follow the same principles as for adult patients.

* The dosage and number of subsequent doses are largely dependent on the method of the RCT and should be based on serum vancomycin levels and residual renal function. Depending on the clinical situation, the next dose may be withheld until vancomycin levels are available.

Liver failure

No dose adjustment is required for patients with hepatic impairment.

Pregnancy

Significantly higher doses may be required to achieve therapeutic serum concentrations in pregnant women (see section "Use during pregnancy or lactation").

Obese patients

For obese patients, the initial dose should be individualized according to total body weight, as for non-obese patients.

Oral administration

Patients aged 12 years and over

Treatment of Clostridioides difficile infection (CDI): The recommended dose of vancomycin is 125 mg every 6 hours for 10 days for a first episode of mild CDI. This dose may be increased to 500 mg every 6 hours for 10 days for severe or complicated disease. The maximum daily dose should not exceed 2 g.

For patients with multiple relapses, treatment of the current episode of CDI with vancomycin 125 mg four times daily for 10 days followed by a taper, i.e., a gradual reduction to 125 mg daily, or a pulse regimen, i.e., 125–500 mg/day every 2–3 days for at least 3 weeks, may be considered.

Newborns, infants and children under 12 years of age

The recommended dose of vancomycin is 10 mg/kg orally every 6 hours for 10 days. The maximum daily dose should not exceed 2 g.

The duration of vancomycin treatment can be tailored to the clinical course of CDI in individual patients. If possible, the antibacterial agent likely to have caused the CDI should be discontinued.