Prescribing Information

INDICATIONS AND CLINICAL USE

Vancoplus is indicated for the treatment of serious or severe infections caused by susceptible strains of Gram-positive (including methicillin-resistant strains) and Gram-negative pathogens.

Complicated skin and skin-structure infections (including cellulitis, myositis and necrotizing fasciitis) caused by:

  • Staphylococcus aureus
  • Staphylococcus epidermidis
  • Streptococcus pyogenes
  • Viridans group streptococci
  • Escherichia coli
  • Enterobacter cloacae
  • Klebsiella oxytoca
  • Klebsiella pneumoniae
  • Proteus mirabilis
  • Morganella morganii
  • Serratia marcescens
  • Bacteroides fragilis

Empirical therapy in meningitis, central nervous system (CNS) infection like brain abscess, suppurative intra cranial infections and Epidural abscess Meningitis caused by:

  • Haemophilus influenzae
  • Neisseria meningitidis
  • Streptococcus pneumoniae
  • Staphylococcus epidermidis
  • Escherichia coli

Prophylaxis of shunt infections:

  • Staphylococcus aureus including MRSA.
  • Staphylococcus epidermidis

CONTRAINDICATIONS

  • Vancoplus is contraindicated in patients with known allergy to the cephalosporin class of antibiotics or vancomycin or any other ingredient of the medicinal product including Larginine.
  •  Vancomycin solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Dosing Considerations & Recommended Dose

Vancoplus is recommended twice daily not less than three days by slow intravenous infusion over 60 minutes. It is not to be diluted with calcium containing solutions

Dosage Adjustment

Hepatic dysfunction:-
Vancoplus dose adjustment is not needed for patients with hepatic dysfunction.

Renal dysfunction: The major route of elimination of active components of Vancoplus component i.e., vancomycin and ceftriaxone is through kidneys. Approximately, 50-60 % of ceftriaxone and 90% of vancomycin is eliminated in urine and the rest is excreted via the bile into the faeces. In general, renal impairment decreases the clearance of the drug and thus increasing the accumulation of drugs which are primarily eliminated by kidneys. Therefore; less dosage is needed for achieving the same therapeutic effect.
Special patient groups
Elderly: These dosages do not require modification in elderly patients provided that renal and hepatic functions are satisfactory. However, dosage reduction may be necessary to a greater extent than expected because of decreasing renal function and auditory function should be monitored.

Patients with impaired renal function: Dosage adjustments must be made to avoid toxic serum levels. In premature infants and the elderly, greater dosage reductions than expected may be necessary because of decreased renal function. Regular monitoring of serum levels is advised in such patients, as accumulation has been reported, especially after prolonged therapy.

Patients with hepatic impairment: No dosage adjustment is required if provided renal function is normal. If the patient has hepatic and renal impairment together than the dose will be adjusted.
Dosage adjustments in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the Vancoplus dosage should be adjusted

Missed Dose:

One should not administer a double dose to make up for a missed one.

Administration:

Vancoplus is recommended by slow intravenous infusion over 60 minutes and it should not be diluted with calcium containing solutions.
In critically ill conditions, for the indications where the amount of infusion cannot be higher, Vancoplus 1.5 g can be diluted in minimum 100ml of the infusion. Similarly for Vancoplus 3 g can be diluted in minimum 200 mL of the infusion. Once reconstituted, Vancoplus should be used immediately. The color may get darkened during storage but it does not affect the efficacy of product if stored up to 24 h at refrigerated condition and up to 12 h at room temperature.

OVERDOSAGE

In the case of over dosage of Vancoplus, nausea, vomiting, diarrhoea can occur. Supportive care is advised, with maintenance of glomerular filtration. Ceftriaxone and vancomycin are poorly removed from the blood by hemodialysis or peritoneal dialysis. Haemoperfusion with Amberlite resin XAD-4 has been reported to be of limited benefit for vancomycin removal. Hemofiltration effectively removes vancomycin from the blood.

Warning & precautions

Hypersensitivity reactions
Before therapy with Vancoplus is instituted, careful inquiry should be made to determine whether the patient has had any previous hypersensitivity reactions to ceftriaxone, any other cephalosporin, or to any penicillin or other beta lactam drug. This product should be given cutaneously to test penicillin-sensitive patients or to any patients who has demonstrated some form of allergy. If an allergic reaction occurs, Vancoplus should be discontinued and the appropriate therapy instituted.

Infusion related reactions
Rapid bolus administration of Vancoplus (e. g. over several minutes) may be associated with exaggerated hypotension, including shock and rarely cardiac arrest. Vancoplus should be administered over a period of not less than 60 minutes to avoid rapid-infusion-related reactions. Stopping the infusion usually results in prompt cessation of these reactions. Vancoplus should be used with caution in patients with renal insufficiency because the risk of toxicity is appreciably increased by high, prolonged blood concentrations of Vancomycin.
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 Vancoplus as a 60 minute infusion prior to anesthetic induction.

Administration site reactions
Vancomycin is irritating to tissue and must be given by a secure intravenous route of administration. Pain, tenderness, and necrosis occur with inadvertent extravasation. Thrombophlebitis may occur, the frequency and severity of which can be minimized by slow infusion of Vancoplus and by rotation of venous access sites. The safety and efficacy of Vancoplus administered by the intrathecal (intralumbar or intraventricular) route or by the intraperitoneal route have not established.

Interaction with calcium-containing products
Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution to reconstitute Vancoplus vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Vancoplus is mixed with calcium-containing solutions in the same IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, Vancoplus and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid. In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of ceftriaxone-calcium.

Clostridium difficile associated diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, therefore it is important to consider its diagnosis in patients who develop diarrhea in association with antibiotic use.

Hemolytic Anemia
An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class of antibacterials including ceftriaxone. Severe cases of hemolytic anemia, including fatalities, have been reported during treatment in both adults and children. If a patient develops anemia while on Vancoplus, the diagnosis of a cephalosporin associated anemia should be considered and Vancoplus should be stopped until the etiology is determined.

Ototoxicity

Ototoxicity has occurred in patients receiving Vancomycin. 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. Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity.

Alteration in prothrombin time

Alterations in prothrombin times have occurred rarely in patients treated with Ceftriaxone. Patients with impaired vitamin K synthesis or low vitamin K stores (e. g, chronic hepatic disease and malnutrition) may require monitoring of prothrombin time during Vancoplus treatment. Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy.

Neutropenia

Reversible neutropenia has been reported in patients receiving Vancomycin. Patients who will undergo prolonged therapy or those who are receiving concomitant drugs that may cause neutropenia should have periodic monitoring of the leukocyte count.

Prolonged use of medicinal product

Prolonged use of Vancoplus may result in overgrowth of non-susceptible organisms. Careful observation of the patient is essential. If super infection occurs during therapy, appropriate measures should be taken.

Hepatic effects

There have been reports of sonographic abnormalities in the gallbladder of patients treated with ceftriaxone; some of these patients also had symptoms of gallbladder disease. These abnormalities appear on sonography as an echo without acoustical shadowing suggesting sludge or as an echo with acoustical shadowing which may be misinterpreted as gallstones. The chemical nature of the sonographically detected material has been determined to be predominantly a ceftriaxone-calcium salt. The condition appears to be transient and reversible upon discontinuation of Ceftriaxone and institution of conservative management. Therefore, Vancoplus should be discontinued in patients who develop signs and symptoms suggestive of gallbladder disease and/or the sonographic findings described above.
Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported rarely in patients treated with ceftriaxone. Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, and total parenteral nutrition). A cofactor role of ceftriaxone related biliary precipitation cannot be ruled out.

General precautions

  •  Doses should be adjusted in patients with marked decrease in the renal function to compensate for reduced clearance.
  •  Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the Vancoplus dosage should be adjusted
  • In order to minimize the risk of nephrotoxicity serial monitoring of renal function should be performed and particular care should be taken in following appropriate dosing schedules.

Special population

Pregnancy:

A moderate amount of data on pregnant women pregnancy outcomes indicates no malformative or feto/neonatal toxicity. In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin hydrochloride on infants were evaluated when the drug was administered to pregnant women for serious staphylococcal infections complicating intravenous drug abuse. Vancomycin hydrochloride was found in cord blood. No sensorineural hearing loss or nephrotoxicity attributable to vancomycin was noted. One infant, whose mother received vancomycin in the third trimester, experienced conductive hearing loss that was not attributable to vancomycin. Because vancomycin was administered only in the second and third trimesters, it is not known whether it causes foetal harm. Animal studies do not indicate reproductive toxicity. Blood levels should be monitored carefully to minimize the risk of foetal toxicity. Ceftriaxone crosses the placental barrier. Safety in human pregnancy has not been established. Reproductive studies in animals have shown no evidence of embryo toxicity, fetotoxicity, teratogenicity or adverse effects on male or female fertility, birth or perinatal and postnatal development. In primates, no embryo toxicity or teratogenicity has been observed. Therefore Vancoplus should not be used in pregnancy unless absolutely indicated.

Nursing mothers:

Caution should be exercised when Vancoplus is administered to a nursing woman. Vancomycin is excreted in human milk, but at therapeutic doses of vancomycin no effects on the breastfed newborns/infants are anticipated. Caution should be exercised when Vancoplus is administered to a nursing woman. It is unlikely that a nursing infant can absorb a significant amount of vancomycin from its gastro-intestinal tract

Pediatric Use: The data regarding pediatric use of Vancoplus is limited. However, health-care professional discretion is required to use Vancoplus in pediatric population wherein benefit vs risk should be evaluated.

Geriatric Use: The pharmacokinetics of ceftriaxone were only minimally altered in geriatric patients compared to healthy adult subjects, whereas the natural decrement of glomerular filtration with increasing age may lead to elevated vancomycin serum concentrations. Therefore, Vancoplus dosage
schedules should be adjusted in elderly patients.

ADVERSE REACTIONS

The data from phase III studies and post marketing surveillance study suggest that Vancoplus is generally well tolerated. The adverse reactions mainly included injection site reactions (phlebitis), skin rashes, gastrointestinal adverse reactions (nausea, vomiting), headache and chills. All were of mild intensity.
No serious adverse event (SAE) was observed with Vancoplus use.

DRUG INTERACTIONS

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 cisplatin, when indicated, requires careful monitoring. In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and ceftriaxone. The potential of interactions cannot be excluded in one of the common ingredient is an interaction substance for another drugs.
The drug-drug interaction of Vancoplus as fixed dose combination is not being reported.


Vancoplus

Prescribing Information

Prescribing Information