Mersa

VANCOMYCIN

500 mg
Lyophilized Powder for I.V. Infusion

Category:

Description

THE CATHAY DRUG CO., INC.

FORMULATION

Each vial (lyophilized powder for I.V. Infusion) contains vancomycin hydrochloride equivalent to 500 mg of vancomycin activity

CLINICAL PHARMACOLOGY

Mechanism of Action

The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Normally this is a five-point interaction. This binding of vancomycin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.

PHARMACOKINETICS

In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin (15 mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mcg/mL immediately after the completion of infusion, mean plasma concentrations of approximately 23 mcg/mL 2 hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL 11 hours after the end of the infusion. Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations of about 49 mcg/mL at the completion of infusion, mean plasma concentrations of about 19 mcg/mL 2 hours after infusion, and mean plasma concentrations of about 10 mcg/mL 6 hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose.

The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is about 0.058 L/kg/h and mean renal clearance is about 0.048 L/kg/h. renal dysfunction slows excretion of vancomycin. In anephric patients, the average half-life of elimination is 7.5 days. The distribution coefficient is from 0.3 to 0.43 L/kg. There are no apparent metabolisms of the drug.

Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. After IV administration of vancomycin, inhibitory concentrations are present in pleural, pericardial, ascetic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs.

INDICATIONS

Vancomycin (MERSA) is an antibiotic used for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (β-lactam-resistant) staphylococci. It belongs to the group of glycopeptide antibiotics. It works by destroying bacteria that cause infections. It is used for the treatment of severe infections, such as those of the heart, bones, brain and cerebral membranes, skin and soft tissues, pneumonia and blood poisoning (sepsis), caused by the staphylococci bacteria, when they are difficult to treat with the usual antibiotics, such as penicillins. It is also used in patients who are allergic to penicillin and cephalosporin antibiotics, for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or cephalosporins, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. Vancomycin (MERSA) is also used for the treatment of severe diarrhea and for the prevention of infections during some operations and other interventions.

DOSAGE AND ADMINISTRATION

Vancomycin (MERSA) is administered via an intravenous infusion and not in the form of a bolus injection or intramuscularly. In certain cases it can also be administered orally.

Parenteral use

Adults

The usual intravenous daily dose for adults is 2 g. It is administered in 2 or 4 equal doses, i.e. 500 mg every 6 hours or 1 g every 12 hours. The medicinal product should be injected slowly, at a maximum rate of 10 mg/minute, over at least 60 minutes or even longer. Vancomycin (MERSA) concentration in the reconstituted solution should not exceed 5 mg/mL in elderly patients, the dose should usually be reduced.

Children

New-born infants aged up to 7 days: the initial dose is 15 mg/kg, followed by 10 mg/kg every 12 hours.

New-born infants aged between 7 days and 1 month: the initial dose is 15 mg/kg, followed by 10 mg/kg every 8 hours.

Children older than 1 month: 10 mg/kg every 6 hours (i.e. 40 mg/kg/day)

Vancomycin (MERSA) concentration in the reconstituted solution used for administration to children should not exceed 2.5 to 5 mg/mL. The medicinal product should be injected for 60 minutes or longer.

The maximum individual dose for children is 15 mg/kg; the maximum daily dose of 60 mg/kg of body weight should not exceed the daily dose for adults.

In new-born infants, monitoring of serum concentrations of vancomycin is recommended. In pre-term new-born infants, the dose should be reduced because of reduced renal function.

DOSAGE IN PATIENTS WITH RENAL FUNCTION IMPAIRMENT

In patients with renal impairment, the dose of the medicinal product and/or interval between the doses should be adjusted to the degree of impairment. Due to the variability of vancomycin’s pharmacokinetics in patients with renal impairment, treatment should be monitored by determining serum concentrations of the medicinal product. The dose of vancomycin is in a linear relationship with creatinine clearance. The daily dose of vancomycin can be determined from the table below based on the patient’s creatinine clearance.

In addition to once daily dosage according to the above table, doses of 250 mg to 1000 mg may also be used. The initial dose is 15 mg/kg of body weight, with which a therapeutic serum concentration will be achieved quickly. The intervals between the doses should be determined based on the measured serum concentrations of vancomycin. In anuric patients, 1000 mg every 7 to 10 days will usually suffice.

PREPARATION OF THE INFUSION SOLUTION

Dissolve a 500 mg dose of Vancomycin (MERSA) in 10 mL of water for injection, or 1 g of Vancomycin (MERSA) in 20 mL of water of injection. One mL of reconstituted solution contains 50 mg of Vancomycin (MERSA). Solution prepared in this manner may be stored for 24 hours at 25°C or for 96 hours in a refrigerator (2°C to 8°C). This solution should be diluted further, depending on the method of administration.

Intermittent infusion: dissolve with 100 or 200 mL of 5% glucose solution or 0.9% sodium chloride solution. The concentration of Vancomycin (MERSA) in the reconstituted solution should not exceed 5 mg/mL. Inject slowly, at a rate of 10 mg/min (at a maximum), for at least 60 minutes or even longer.

Continuous infusion: this should only be used if treatment with an intermittent infusion is not possible. Dilute 1 to 2 g of dissolved Vancomycin (MERSA) in a sufficient amount of 5% glucose or 0.9% sodium chloride solution and administer it in the form of a drip solution, so that the patient will receive the prescribed daily dose in 24 hours.

Stability of the reconstituted solution

Vancomycin (MERSA) solutions diluted with 5% glucose or 0.9% sodium chloride may be stored in a refrigerator for 14 days without significant loss of potency. Solutions diluted with the following infusion fluids, however, may be stored in a refrigerator for only 96 hours:

  • 5% glucose and 0.9% sodium chloride
  • Ringer’s Lactate
  • Ringer’s Acetate
  • Ringer’s Lactate and 5% glucose

MONITORING OF SERUM CONCENTRATIONS

The desired maximum serum concentrations of Vancomycin (MERSA), measured 2 hours after completed infusion, range between 20 and 30 mg/L.

The desired maximum concentrations, measured just before the next dose, range between 5 and 10 mg/L.

The nephrotoxicity of Vancomycin (MERSA) mainly occurs at the lowest serum concentrations of 10 mg/L or more. Ototoxicity rarely occurs at serum concentrations lower than 30 mg/L.

CONTRAINDICATIONS

Do not use Vancomycin (MERSA) if you are allergic to vancomycin or any of its components.

WARNINGS

Rapid bolus administration (i.e., over several minutes) may be associated with exaggerated hypotension including shock and rarely, cardiac arrest.

Vancomycin hydrochloride should be administered in a diluted solution over a period of not less than 60 minutes to avoid rapid-infusion-related reactions. Stopping the infusion usually results in a prompt cessation of these reactions.

Ototoxicity has occurred in patients receiving vancomycin hydrochloride. It may be transient or permanent. It has been reported mostly in patients who have been given excessive doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent such as an aminoglycoside. Vancomycin should be used with caution in patients with renal insufficiency because the risk of toxicity is appreciably increased by high, prolonged blood concentrations.

PRECAUTIONS

Take special care with Vancomycin (MERSA) in:

  • Prescribing Vancomycin (MERSA) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patients and increases the risk of the development of drug-resistant bacteria.
  • Prolonged use of Vancomycin (MERSA) may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken. In rare instances, there have been reports of pseudomembranous colitis due to C. difficile developing in patients receiving IV vancomycin.
  • In order to minimize the risk of nephrotoxicity when treating patients with underlying renal dysfunction or patients receiving concomitant therapy with an aminoglycoside, serial monitoring of renal function should be performed and particular care should be taken in following appropriate dosing schedules.
  • Series of auditory function may be helpful in order to minimize the risk of ototoxicity.
  • Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride. Patients who will undergo prolonged therapy with vancomycin hydrochloride or those who are receiving concomitant drugs which may cause neutropenia should have periodic monitoring of the leukocyte count.
  • There have been reports that the frequency of infusion-related events (including hypotension, flushing, erythema, urticaria and pruritus) increases with the concomitant administration of anesthetic agents. Infusion-related events may be minimized by the administration of vancomycin as a 60 minute infusion prior to anesthetic induction.
  • Vancomycin (MERSA) solution should not be mixed with other solutions or medicines in the same infusion bottle, because this may neutralize the effects of the medicinal product or lead to other changes in the solution. Which, may cause problems during administration of the medicinal product in the blood vessel.

ADVERSE EFFECTS

The most frequent adverse effects of Vancomycin (MERSA) are the so-called “red man syndrome”, which occurs in 5 to 11% of patients, and pain and swelling at the site of injection or inflammation of the blood vessel into which the patients is receiving the medicinal product.

Stop the treatment and seek immediate medical assistance if any of the following occurs:

  • Swelling of the face, lips, mouth, throat or elsewhere in the body, which may cause difficulty in swallowing or breathing
  • Urticaria
  • Loss of consciousness
  • Blisters or peeling of the skin or mucous membranes

These adverse events are very rare, but very serious.

The patient should also need to seek immediate medical assistance is there is severe diarrhea, significantly less or more urine than usual, bloody or otherwise changed urine and lumbar pain. These are serious adverse effects, which are rare, but they nevertheless require medical attention.

Phlebitis, the inflammation at the injection site, has been reported.

DRUG INTERACTIONS

Concomitant administration of vancomycin and anaesthetic agents have been associated with erythema and histamine-like flushing and anaphylactoid reactions.

Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs such as amphotericin B, aminoglycosides, bacitracin, polymixin B, colistin, viomycin, or cisplatin, when indicated requires careful monitoring.

PREGNANCY AND LACTATION

Vancomycin (MERSA) should only be administered during pregnancy only if the potential benefit outweighs the risk. Vancomycin hydrochloride is excreted in human milk. Caution should be exercised when vancomycin hydrochloride is administered to a nursing woman. Because of the potential for adverse events, a decision should be made whether to discontinue nursing or discontinue the drug, taking into consideration the importance of the drug to the mother.

OVERDOSAGE

Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Hemofiltration and hemoperfusion with polysulfone resin have been reported to result in increased vancomycin clearance.

STORAGE

Store at temperatures not exceeding 25°C.

KEEP OUT OF REACH OF CHILDREN.

Do not use after the expiration date.

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