Mersa IV 500/Mersa IV 1000

Mersa IV 500: Mersa IV 500 mg Lyophilized Powder for Injection (IV infusion): Each vial contains: Vancomycin (as hydrochloride), USP 500 mg.
Mersa IV 1000: Mersa IV 1 g Lyophilized Powder for Injection (IV Infusion): Each vial contains: Vancomycin (as hydrochloride), USP 1 g.

Pharmacology: Pharmacokinetics: Absorption and Distribution: In subjects with normal renal function, multiple intravenous dosing of 1 g of Vancomycin (15 mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mg/L immediately after the completion of infusion and mean plasma concentrations of approximately 23 mg/L 2 hours after infusion. Multiple dosing of 500 mg infused over 30 minutes produces a mean plasma concentrations of about 49 mg/L at the completion of infusion, mean plasma concentrations of about 19 mg/L 2 hours after infusion, and mean plasma concentrations of about 10 mg/L 6 hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose.
Metabolism and Elimination: The mean elimination half-life of Vancomycin from the plasma is 4-hours in patients with normal renal function. About 75% of an administered dose of Vancomycin is excreted in urine by glomerular filtration in the first 24 hours.
Mean plasma clearance is about 0.058 L/kg/h and mean renal clearance is about 0.048 L/kg/h. Renal vancomycin clearance is fairly constant and accounts for 70% to 80% of vancomycin elimination. The volume of distribution ranges from 0.39 to 0.97 L/kg. There is no apparent metabolism of the drug. Vancomycin is 55% protein bound as measured by ultrafiltration at vancomycin serum levels of 10 to 100 mg/L.
After IV administration of Vancomycin, inhibitory concentrations are present in pleural, pericardial, ascetic, atrial appendage tissue and synovial fluid, as well as urine and peritoneal fluid.
Vancomycin does not readily penetrate the cerebrospinal fluid unless the meninges are inflamed.

Treatment of potentially life-threatening infections due to susceptible gram-positive organisms which cannot be treated by other effective, less toxic antimicrobial drugs, such as the penicillins and cephalosporins.
Severe staphylococcal infections in patients who cannot receive or who have failed to respond to the penicillins and cephalosporins or who have infections with staphylococci that are resistant to other antibiotics.
Endocarditis and as prophylaxis against endocarditis in patients at risk from dental or surgical procedures.
Other infections due to staphylococci, including osteomyelitis, pneumonia, septicemia and soft tissue infections.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Infusion-related events are related to both the concentration and the rate of administration of Vancomycin (Mersa IV 500 & 1000).
Concentrations of no more than 5 mg/mL and rates of no more than 10 mg/min are recommended in adults. In selected patients in need of fluid restriction, a concentration up to 10 mg/mL may be used. Use of such higher concentrations may increase the risk of infusion-related events. Infusion-related events may occur, however, at any rate or concentration.
Adults: The usual dosage for intravenous infusion is 500 mg as Vancomycin (Mersa IV 500 & 1000) every 6 hours or 1 g as vancomycin (potency) every 12 hours or as prescribed by the physician. Other patient factors, such as age or obesity, may call for modification of the usual daily dose. The total duration of therapy is determined by the type and severity of the infection and the clinical response of the patient. In staphylococcal endocarditis, treatment for three weeks or longer is recommended.
Children: The usual intravenous dosage of Vancomycin (Mersa IV 500 & 1000) is 10 mg/kg per dose given every six hours. Each dose should be administered over a period of at least 60 minutes.
Infants: In both neonates and infants, an initial dose of 15 mg/kg is suggested, followed by 10 mg/kg every 12 hours for neonates in the first week of life and thereafter every eight hours up to the age of one month. Each dose should be administered over 60 minutes. Close monitoring of serum concentrations of Vancomycin (Mersa IV 500 & 1000) may be warranted in these patients (see Table 1).

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Patients with renal impairment and the elderly: In patients with impaired renal function, dosage reduction may be required. In premature infants and the elderly, greater dosage reductions than expected may be necessary because of decrease renal function. See Table 2.

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Table 2 is not valid for functionally anephric patients. For such patients, an initial dose of 15 mg/kg of body weight should be given to achieve prompt therapeutic serum concentrations. The dose required to maintain stable concentrations is 1.9 mg/kg/24 hr. In patients with marked renal impairment, it may be more convenient to give maintenance doses of 250-1000 mg once every several days rather than administering this drug on a daily basis. In anuria, a dose of 1000 mg every 7-10 days has been recommended.
The creatinine clearance is calculated by the following formula: See Equation.
Men: Creatinine clearance = Body weight (kg) x (140-age)/72 x serum creatinine (mg/dL)
Women: 0.85 x men's value
The serum creatinine must represent a steady state of renal function. Such a calculated creatinine clearance is an over estimate of actual clearance in the following cases: Patients with decreased renal function such as shock, severe heart failure or oliguria, patients with abnormal relationship between muscle mass and total body weight such as obesity, liver disease, edema or ascites, patients with debilitation, malnutrition or inactivity.

Symptoms: Renal disorders such as acute renal failure and eighth cranial nerve impairment such as hearing loss may occur.
Measures: Supportive care is advised, with maintenance of glomerular filtration. This drug is poorly removed by dialysis and hemofiltration and hemoperfusion with polysurfone resin have been reported to result in increased clearance of this drug. The median lethal intravenous dose is 319 mg/kg in rats and 400 mg/kg in mice.

Patients with history of shock to this drug.
Patients with history of hypersensitivity to this drug, peptide antibiotics or aminoglycoside antibiotics.

To prevent the emergence of resistant microorganisms by the therapy with the drug, it is desirable to check susceptibility and to administer for the shortest period as possible.
Due to the possibility of developing toxic effects in the presence of the continuously maintained serum concentration and prolonged high blood concentrations, the drug should be used with caution in patients with renal failure with the dosage adjustment. In the treatment of patients with the history of renal disorder and in those who are receiving concomitant treatment with aminoglycosides, serial tests of renal function must be performed and the appropriate dose regimens adhered to in order to reduce the risk of nephrotoxicity to a minimum.
In case of repeated oral administration for the treatment of pseudomembranous colitis by Clostridium difficile, if the sign of improvement of symptoms such as diarrhea, abdominal pain and fever does not appear clearly within 7-10 days, treatment should be discontinued.
Prolonged use may result in the overgrowth of non-susceptible microorganisms. If superinfection occurs during therapy, the drug should be discontinued and appropriate measures should be taken.
Serial tests of auditory function is advisable in order to minimize the risk of ototoxicity.
During therapy, serum test, urine analysis and tests of liver function and renal function should be conducted periodically. Patients who will undergo prolonged therapy with the drug or those who are receiving concomitant drugs that may cause neutropenia should have periodic monitoring of the leukocyte count.

As a rule, the drug should not be administered to patients who have hearing loss by peptide antibiotics or aminoglycoside antibiotics or other underlying hearing loss, but if absolutely necessary, the drug should be used with caution.
Patients with renal impairment such as acute urinary retention (because this drug is accumulated due to delayed excretion, it should be administered cautiously with the monitoring of serum concentration).
Patients with hepatic impairment (hepatic impairment may be caused or deteriorated).
The elderly.
Premature infants, neonates.
Patients with impaired vestibular organ or impaired cochlea.
Precautions in Administration: The drug is irritating to tissue and it must not be given by intramuscular injection. Careless intravenous administration extravasation may cause pain, tenderness on pressure, necrosis, etc.
Thrombophlebitis may occur by intravenous administration with high concentration, but the frequency and severity of which can be minimized by enough dilution (2.5-5 g/L), slow infusion and rotation of venous access sites.
Rapid bolus administration over several minutes may cause hypotension and rarely, cardiac arrest. To avoid rapid-infusion-related reactions, the drug should be administered over a period of not less than 60 minutes. Stopping the infusion usually results in prompt cessation of these reactions.
The safety and efficacy of administration via lumbar vertebrae and cerebral ventricles are not evaluated yet.
Due to the low pH of solution, mixing with other substances may cause physical or chemical instability. Do not mix drug with alkaline solutions.
Solution of the drug and beta-lactam antibiotics are physically incompatible. The likelihood of precipitation increases with higher concentrations of the drug. It is recommended to adequately flush the intravenous lines between administration of these antibiotics. It is also recommended to dilute solutions of the drug to 5 mg/mL or less.
Administration of the drug into the vitreous body is not permitted. A Precipitation has been reported when this drug and ceftazidime were injected into the vitreous body of patients with endophthalmitis using separate syringe and needle. Precipitate gradually dissolved and two months later, vitreous cavity became transparent completely and sight was improved.
Before injection, the drug should be inspected visually for particulate matter and discoloration.
Use in Children: Premature infants, neonates and toddlers are at the stage of renal development. Because high serum concentration may last for a long time due to prolonged half-life in these groups, caution should be taken in the administration.
Use in the Elderly: Due to age-related reduction in renal function, renal function should be tested before and during administration, and the drug should be administered with caution by reducing doses according to the decreased renal function.

In reproduction studies on rats at doses up to 5 times the human dose and rabbits at doses up to 3 times the human dose, fetotoxicity has not been reported.
In a controlled clinical study, the potential ototoxic and nephrotoxic effects of this drug on infants were evaluated when the drug was administered to pregnant women for serious staphylococcal injections. This drug was found in cord blood and no sensorial hearing loss or nephrotoxicity attributable to this drug was noted.
One infant whose mother received this drug in the third trimester experienced conducive hearing loss. Because the number of patients treated in this study was limited and this drug was administered only in the second and third trimesters, it is not known whether this drug causes fetal harm.
Because the safety of this drug during pregnancy has not been established, the drug should be administered to pregnant women or women of child bearing potential only if therapeutic benefit is judged to overweight the potential risk. If administered, serum concentration should be carefully monitored to reduce fetotoxicity.
Because the drug is excreted in human milk, nursing mothers should avoid administration of the drug. If treatment is unavoidable, nursing should be discontinued.

Neuropsychological system: Because shock and anaphylactoid symptom may rarely occur, patients should be monitored closely. If any adverse reaction is observed, administration should be discontinued and appropriate measure should be taken.
Digestive system: Loose feces, diarrhea, nausea, vomiting and abdominal pain may rarely occur.
Blood system: Oligocythemia, leukopenia, thrombocytopenia and eosinophilia may rarely occur.
Reversible neutropenia has been reported and neutropenia appears to be promptly reversible when this drug is discontinued. Although a causal relationship has not been established, reversible agranulocytosis (granulocytes ≤500/mm³) has been reported rarely.
Central nervous system: Because the eighth cranial nerve impairment such as dizziness, tinnitus, hearing loss, etc, may occur, close monitoring is required including testing hearing activity. As a rule, this drug should not be administered to patients with these symptoms, but if absolutely necessary, drug should be used with caution. Hearing loss associated with the drug has been reported in patients who had kidney dysfunction or a preexisting hearing loss or were receiving concomitant treatment with an ototoxic drug.
Liver: Because increased bilirubin, AST, ALT and ALP, rarely increased LDH, γ-GTP and LAP may occur, patients should be observed closely including regular monitoring. If any adverse reaction occurs, appropriate measure should be taken including discontinuation of administration.
Kidney: Because renal impairment such as increase BUN and creatinine may occur, patients should be observed closely including regular monitoring. As a rule, the drug should not be administered to patients with these adverse reactions, but if absolutely necessary, the drug should be used with caution.
Interstitial nephritis have been reported rarely in patients who were given aminoglycoside antibiotics or who had preexisting kidney dysfunction. When the drug was discontinued, azotemia resolved.
Skin: Exfoliative dermatitis, bullous dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis may occur.
Hypersensitivity reactions: When rash, erythema, flushing, hypotension, wheezing, dyspnea, urticarial and pruritus occurs, appropriate measure should be taken. Rapid infusion may also cause red-man's syndrome (erythema, bleeding of face, neck and upper body), pain of chest and abdomen and muscle spasm. These reactions usually resolve within 20 minutes but may persist for several hours. In animal studies where overdose of this drug was administered rapidly with high concentration, hypotension and bradycardia occurred. These adverse reactions rarely occur when the drug is slowly administered over a period not less than 60 minutes, and there was no injection related adverse reactions when this drug was administered to healthy human with a rate of not more than 10 mg/minute.
Others: Occasionally fever, angialgia, phlebitis, rarely, nausea, chills and vasculitis may occur, pseudomembranous colitis by Clostridium difficile also has been reported in patients who had administered the drug intravenously.

The frequency of anaphylactoid reactions including flushing, histamine like response, hypotension, wheezing, dyspnea, urticaria, and pruritus may increase with the concomitant administration of anesthetic agents, it can be minimized by the administration of the drug as a 60-minute infusion prior to anesthetic induction.
Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, or platinum antitumor drugs (cisplatin, nedaplatin, etc) may increase adverse reactions, so it should be administered with caution.
Change of international normalized ratio (INR) in patients taking anticoagulant with antibiotics including the drug concomitantly increased anticoagulant activity has been reported. Infectious disease (accompanied with inflammatory process) and age and general condition of patients are risk factors. Although interaction of the drug with warfarin has not been established through clinical trials, INR monitoring should be performed and if necessary, the dosage of oral anticoagulant should be properly adjusted. Some kinds of antibiotics, especially fluoroquinolones, macrolides, cyclins, cotrimoxazole and some cephalosporins showed severe cases.

Special Precaution for Disposal and Other Handling: For single use. Discard any unused contents.
500 mg: Preparation of Solution: At the time of use, add 10 mL of Sterile Water for Injection to a 500 mg vial of Vancomycin (Mersa IV 500) Lyophilized Powder for Injection (IV Infusion). Vials reconstituted in this manner will give a solution of 50 mg/mL.
1 g: Preparation of Solution: At the time of use, add 20 mL of Sterile Water for Injection to a 1 g vial of Vancomycin (Mersa IV 1000) Lyophilized Powder for Injection (IV Infusion).
Further dilution is required depending on method of administration: Intermittent infusion (the preferred method of administration): Reconstituted solutions containing 500 mg Vancomycin (Mersa IV 500) must be diluted with at least 100 mL diluent.
Reconstituted solutions containing 1 g Vancomycin (Mersa IV 1000) must be diluted with at least 200 mL diluent.
Sodium Chloride 0.9% Intravenous Infusion or 5% Dextrose Intravenous Infusion are suitable diluents. The desired dose should be administered by intravenous infusion over a period of at least 60 minutes. If administered over a shorter period of time or in higher concentrations, there is a possibility of inducing marked hypotension in addition to thrombophlebitis.
Rapid administration may also produce flushing and a transient rash over the neck ad shoulders.
Continuous infusion (should only be used when intermittent infusion not feasible): 1 g or 2 g of Vancomycin (Mersa IV 500 & 1000) may be added to a sufficiently large volume of Sodium Chloride 0.9% Intravenous Infusion or 5% Dextrose Intravenous Infusion to permit the desired dose to be infused over twenty-four hours.

Prior to reconstitution, vials should be stored at temperatures not exceeding 30°C. Reconstituted solution should be stored between 2-8°C. Protect from light.

Other Antibiotics

J01XA01 - vancomycin ; Belongs to the class of glycopeptide antibacterials. Used in the systemic treatment of infections.

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