ADVENT I.V. Injection (Amoxycillin sodium + Clavulanic acid)

Table of Content

Composition

ADVENT 1.2 gm Injection

Each vial contains

Amoxycillin Sodium IP equivalent to Amoxycillin .................1,000 mg

Potassium Clavulanate IP equivalent to Clavulanic acid ....... 200 mg

ADVENT 600 mg Injection

Each vial contains

Amoxycillin Sodium IP equivalent to Amoxycillin .....................500 mg

Potassium Clavulanate IP equivalent to Clavulanic acid ....... 100 mg

ADVENT 300 mg Injection

Each vial contains

Amoxycillin Sodium IP equivalent to Amoxycillin .....................250 mg

Potassium Clavulanate IP equivalent to Clavulanic acid ...........50 mg

ADVENT 150 mg Injection

Each vial contains

Amoxycillin Sodium IP equivalent to Amoxycillin .....................125 mg

Potassium Clavulanate IP equivalent to Clavulanic acid ...........25 mg

Dosage form

Powder for reconstitution for injection or infusion

Pharmacology

Pharmacodynamics

ADVENT I.V. is a formulation of amoxycillin and clavulanic acid. Amoxycillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by

cell lysis and death. Amoxycillin is, however, susceptible to degradation by beta-lactamases and, therefore, the spectrum of activity does not include organisms that produce these enzymes.

Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated beta-lactamases frequently responsible for transferred drug resistance. However, clavulanic acid alone does not exert a clinically useful antibacterial effect.

The formulation of amoxycillin and clavulanic acid in ADVENT I.V. protects amoxycillin from degradation by beta-lactamase enzymes and effectively extends the antibiotic spectrum of amoxycillin to include many bacteria normally resistant to amoxycillin and other beta-lactam antibiotics. Thus, ADVENT I.V. possesses the properties of a broad-spectrum antibiotic and a beta-lactamase inhibitor.

ADVENT I.V. is bactericidal to a wide variety of organisms, including the following:

Gram-positive

Aerobes

Bacillus anthracis,* Corynebacterium species, Enterococcus faecalis,* Enterococcus faecium,* Listeria monocytogenes, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridians, Streptococcus agalactiae, Streptococcus species, Staphylococcus aureus,* Coagulase-negative staphylococci* (including Staphylococcus epidermidis)

Anaerobes

Clostridium species, Peptococcus species, Peptostreptococcus species

Gram-negative

Aerobes

Bordetella pertussis, Brucella species, Escherichia coli,* Gardnerella vaginalis, Haemophilus influenzae, Helicobacter pylori, Klebsiella species,* Legionella species, Moraxella catarrhalis,* (Branhamella catarrhalis), Neisseria gonorrhoeae,* Neisseria meningitidis,* Pasteurella multocida, Proteus mirabilis,* Proteus vulgaris,* Salmonella species,* Shigella species,* Vibrio cholerae, Yersinia enterocolitica*

Anaerobes

Bacteroides species* (including B.fragilis), Fusobacterium species*

 *Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxycillin alone.

Infections caused by amoxycillin-susceptible organisms are amenable to ADVENT I.V.  treatment due to its amoxycillin content. Mixed infections caused by amoxycillin-susceptible organisms in conjunction with amoxycillin/clavulanic acid susceptible beta-lactamase-producing organisms may therefore be treated with amoxycillin/clavulanic acid.

Pharmacokinetics

The pharmacokinetic results for studies in which amoxycillin/clavulanic acid was administered to groups of healthy volunteers as either 500 mg/100 mg or 1,000 mg/200 mg given as a bolus I.V. injection are presented below.

Mean (±SD) Pharmacokinetic Parameters Bolus I.V. Injection

Dose administered

Amoxycillin

Dose

Mean peak serum concentration (μg/ml)

T ½(h)

AUC (h.mg/l)

Urinary recovery (%, 0–6 hours)

AMX/CA 500 mg/100 mg

500 mg

32.2

1.07

25.5

66.5

AMX/CA 1,000 mg/200 mg

1,000 mg

105.4

0.9

76.3

77.4

 

Clavulanic acid

AMX/CA 500 mg/100 mg

100 mg

10.5

1.12

9.2

46.0

AMX/CA 1,000 mg/200 mg

200 mg

28.5

0.9

27.9

63.8

AMX/CA: Amoxycillin/clavulanic acid

DUC (h.n dioxide in expired air.About 25% of total plasma clavulanic acid and 18% of total plasma amoxycillin is bound to protein. The apparent volume of distribution is around 0.3–0.4 l/kg for amoxycillin and around 0.2 l/kg for clavulanic acid.

Following I.V. administration, both amoxycillin and clavulanic acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxycillin does not adequately distribute into the cerebrospinal fluid.

From animal studies, there is no evidence for significant tissue retention of drug-derived material for either component. Amoxycillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanic acid can also be detected in breast milk. Amoxycillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10–25% of the initial dose. Clavulanic acid is extensively metabolized in humans, and eliminated in the urine and faeces and as carbon dioxide in expired air.

The major route of elimination for amoxycillin is via the kidneys, whereas for clavulanic acid, it is by both renal and non-renal mechanisms.

Amoxycillin/clavulanic acid has a mean elimination half-life of approximately 1 hour and a mean total clearance of approximately 25 l/hour in healthy subjects. Approximately 60 to 70% of the amoxycillin and approximately 40–65% of the clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of a single 500/100 mg or a single 1,000/200 mg bolus I.V. injection. Various studies have found the urinary excretion to be 50–85% for amoxycillin and between 27% and 60% for clavulanic acid over a 24-hour period. In the case of clavulanic acid, the largest amount of drug is excreted during the first 2 hours after administration.

Age

The elimination half-life of amoxycillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life, the interval of administration should not exceed twice-daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Renal Impairment

The total serum clearance of amoxycillin/clavulanic acid decreases proportionately with decreasing renal function. The reduction in drug clearance is more pronounced for amoxycillin than for clavulanic acid, as a higher proportion of amoxycillin is excreted via the renal route. Doses in renal impairment must, therefore, prevent undue accumulation of amoxycillin while maintaining adequate levels of clavulanic acid.

Hepatic Impairment

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.

Indications

ADVENT I.V. is indicated for:

1.    Treatment of the following infections in adults and children:

  • ·         Severe upper respiratory tract infections of the ear, nose and throat (such as mastoiditis, peritonsillar infections, epiglottitis and sinusitis when accompanied by severe systemic signs and symptoms).
  • ·            Lower respiratory tract infections, e.g. community-acquired pneumonia, acute exacerbations of chronic bronchitis (adequately diagnosed).
  • ·            Genito-urinary tract infections, e.g. cystitis, pyelonephritis.
  • ·            Skin and soft tissue infections, e.g. cellulitis, animal bites, severe dental abscess with spreading cellulitis.
  • ·            Bone and joint infections, e.g. osteomyelitis.
  • ·            Intra-abdominal infection.
  • ·            Female genital infections

2.  Prophylaxis against infections associated with major surgical procedures in adults, such as those involving the gastrointestinal tract, pelvic cavity, head and neck, biliary tract surgery.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Dosage and Administration

Dosage

ADVENT I.V. may be administered either by I.V. injection or intermittent infusion. It is not suitable for intramuscular administration.

Usual Dosages for the Treatment of Infection

 

Children

(aged 0–3 months)

 

Children

(aged 3 months–12 years)

 

Adults and Children (aged over 12 years)

30 mg/kg* ADVENT I.V. every 12 hours in premature infants and in full-term infants during the perinatal period, increasing to 8 hours thereafter.

Usually 30 mg/kg* ADVENT I.V. 8-hourly. In more serious infections, increase frequency to 6-hourly intervals.

 

 

Usually 1.2 g thrice daily. In more serious infections, increase frequency to 6- hourly intervals.

*Each 30 mg of ADVENT I.V. provides 25 mg amoxycillin and 5 mg clavulanic acid. Therapy can be started parenterally and continued with the oral preparation of ADVENT.

The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be extended beyond 14 days without review.

Dosage for Surgical Prophylaxis

Adults and Children ≥40 kg

  • ·         For procedures less than 1 hour in duration, the recommended dose of ADVENT I.V.  is 1.2 g given at the induction of anaesthesia.
  • ·         For procedures greater than 1 hour in duration, the recommended dose of ADVENT I.V. is 1.2 g given at the induction of anaesthesia, with up to three doses of 1.2 g in 24 hours.
  • ·         Operations where there is a high risk of infection, e.g. colorectal surgery, may require three, and up to four, doses of 1.2 g ADVENT I.V. in a 24-hour period. These doses are usually given at 0, 8, 16 (and 24) hours. This regimen can be continued for several days if the procedure has a significantly increased risk of infection.

Clear clinical signs of infection at operation will require a normal course of I.V. or oral ADVENT therapy post-operatively.

Renal Impairment

Adults and Children (≥40 kg)

Renal Impairment

Recommended Dosage for Patients with Renal Impairment

Mild Impairment (creatinine clearance >30 mL/min

 

                          No change in dosage

Moderate Impairment (CrCl 10–30 mL/min)

 

1.2 g I.V. stat. followed by 600 mg I.V. q12h

Severe Impairment/ Haemodialysis

(CrCl <10 mL/min)

1.2 g I.V stat. followed by 600 mg I.V. q24h
 

Dialysis decreases serum concentrations of ADVENT I.V. and an additional 600 mg I.V. dose may need to be given during dialysis and at the end of dialysis

*Each 30 mg of ADVENT I.V. provides 25 mg amoxycillin and 5 mg clavulanic acid. Therapy can be started parenterally and continued with the oral preparation.

Children <40 kg

CrCl: 10–30 mL/min

25 mg/5 mg per kg given every 12 hours

CrCl <10 mL/min

25 mg/5 mg per kg given every 24 hours

Haemodialysis

25 mg/5 mg per kg given every 24 hours, plus a dose of 12.5 mg/2.5 mg per kg at the end of dialysis (as serum concentrations of both amoxycillin and clavulanic acid are decreased).

Hepatic Impairment

Dose with caution; monitor hepatic function at regular intervals.

Preparation

1.2 g vial: To reconstitute, dissolve contents in 20 mL of Sterile Water for Injection, IP, (final volume: 20.9 mL).

600 mg vial: To reconstitute, dissolve contents in 10 mL of Sterile Water for Injection, IP, (final volume: 10.5 mL).

300 mg vial: To reconstitute, dissolve contents in 5 mL of Sterile Water for Injection, IP, (final volume: 5.25 mL).

150 mg vial: To reconstitute, dissolve contents in 2.5 mL of Sterile Water for Injection, IP, (final volume: 2.625 mL).

Reconstituted solutions of Advent are normally colourless or a pale, straw colour. The solution is to be inspected visually for particulate matter and discoloration prior to administration. It should only be used if the solution is clear and free from particles. Do not use if solution is not clear/ hazy after reconstitution.

For I.V. Injection

The stability of ADVENT I.V. solution is concentration-dependent; thus, ADVENT I.V. should be used immediately upon reconstitution and given by slow I.V. injection over a period of 3–4 minutes. ADVENT I.V. may be injected directly into a vein or via a drip tube. ADVENT I.V. is not suitable for intramuscular administration.

For I.V. Infusion

ADVENT I.V. may be infused in Sterile Water for Injection, IP, or Sodium Chloride I.V. Injection, IP, (0.9% w/v). Without delay,* add 1.2 g, 600 mg, 300 mg, and 150 mg reconstituted solution to 100 mL, 50 mL, 25 mL, and 12.5 mL of infusion fluid, respectively. Infuse over 30–40 minutes and complete within 4 hours of reconstitution.

*Solutions should be made up to full infusion volume immediately after reconstitution. Any residual antibiotic solutions should be discarded.

Children aged less than 3 months should be administered ADVENT I.V. by infusion only.

Reconstituted ADVENT I.V. solutions should be used or diluted immediately within 20 minutes.

Stability and Compatibility

Infusions of ADVENT I.V. should be given with the I.V. fluids mentioned below. Satisfactory antibiotic concentrations are retained at 5°C and at room temperature (25°C) in the recommended volumes of the following infusion fluids. If reconstituted and maintained at room temperature, infusions should be completed within the times stated.

I.V. infusion fluids                                                                        Stability period: 25°C

  Sterile Water for Injection, IP                                                     4 hours

  Sodium Chloride I.V. Infusion, IP, (0.9% w/v)                           4 hours

  Compound Sodium Chloride I.V. Infusion, IP                           3 hours

  (Ringer’s solution)

Reconstituted solutions should not be frozen.

Amoxycillin/clavulanic acid is less stable in infusions containing glucose, dextran or bicarbonate. Reconstituted solutions of ADVENT I.V. should, therefore, not be added to such infusions but may be injected into the drip tubing, over a period of 3–4 minutes.

For storage at 5°C, the reconstituted solution should be added to pre-refrigerated infusion bags, which can be stored for up to 8 hours. Thereafter, the infusion should be administered immediately after reaching room temperatures.

I.V. Infusion Fluids                                                                    Stability Period: 5°C

  Sterile Water for Injection, IP                                                             8 hours

  Sodium Chloride I.V. Infusion, IP, (0.9% w/v)                                   8 hours
 

Any residual antibiotic solution should be discarded.

Contraindications

Amoxycillin/clavulanic acid is contraindicated in patients with penicillin hypersensitivity. Attention should be paid to possible cross-sensitivity with other beta-lactam antibiotics, e.g. cephalosporins. It is also contraindicated in patients with a previous history of amoxycillin/clavulanic acid associated jaundice/hepatic dysfunction.

Warnings and Precautions

Before initiating therapy with amoxycillin/clavulanic acid, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents.

Serious and, occasionally, fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxycillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.

Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Changes in liver function test have been observed in some patients receiving amoxycillin/clavulanic acid. The clinical significance of these changes is uncertain, but amoxycillin/clavulanic acid should be used with caution in patients with evidence of hepatic dysfunction.

Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. In all populations, signs and symptoms usually occur during or shortly after treatment but, in some cases, may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and in extremely rare circumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects.

Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for several weeks after treatment has ceased.

Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function, is advisable during prolonged therapy.

Amoxycillin/clavulanic acid should be avoided if infectious mononucleosis is suspected since the occurrence of morbilliform rash has been associated with this condition following the use of amoxycillin.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.

Erythematous rashes have been associated with glandular fever in patients receiving amoxycillin. Amoxycillin/clavulanic acid should be avoided if glandular fever is suspected. The occurrence at the treatment initiation of a feverish generalized erythema associated with pustula may be a symptom of acute generalized exanthemous pustulosis (AGEP). This reaction requires amoxycillin/clavulanic acid discontinuation and contraindicates any subsequent administration of amoxycillin.

Prolonged use may also occasionally result in the overgrowth of non-susceptible organisms.

Antibiotic-associated colitis has been reported with nearly all antibacterial agents, including amoxycillin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, amoxycillin/clavulanic acid should immediately be discontinued, a physician be consulted and an appropriate therapy initiated. Anti-peristaltic drugs are contraindicated in this situation.

If the parenteral administration of high doses is necessary, the sodium content must be taken into account in patients on a sodium-restricted diet.

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxycillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxycillin crystalluria.

When present at high concentrations in urine at room temperature, amoxycillin may precipitate in bladder catheters. A regular check on patency should be maintained.

Prolongation of prothrombin time has been reported rarely in some patients receiving amoxycillin/clavulanic acid and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

In the case that an infection is proven to be due to an amoxycillin-susceptible organism(s), then consideration should be given to switching from amoxycillin/clavulanic acid to amoxycillin in accordance with official guidance.
This presentation of amoxycillin/clavulanic acid may not be suitable for use when there is a high risk that the presumptive pathogens have resistance to beta-lactam agents that are not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. As no specific data for T>MIC are available and the data for comparable oral presentations are borderline, this presentation (without additional amoxycillin) may not be suitable for the treatment of penicillin-resistant Streptococcus pneumoniae.
During treatment with amoxycillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false-positive results may occur with non-enzymatic methods.

Clavulanic acid may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false-positive Coombs test.

There have been reports of positive test results using the Aspergillus EIA test in patients receiving amoxycillin/clavulanic acid who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving amoxycillin/clavulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.

Drug Interactions

Probenecid: Co-administration of probenecid cannot be recommended. Probenecid decreases the renal tubular secretion of amoxycillin. Concomitant use with amoxycillin/clavulanic acid may result in increased and prolonged blood levels of amoxycillin but not of clavulanic acid.

Anticoagulants: Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. In the literature, there are rare cases of increased international normalized ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxycillin. If co-administration is necessary, the prothrombin time or international normalized ratio should be carefully monitored with the addition or withdrawal of amoxycillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary

Allopurinol: The concomitant use of allopurinol during treatment with amoxycillin can increase the likelihood of allergic skin reactions.  There are no data with amoxycillin/clavulanic acid and allopurinol administered concurrently.

Methotrexate: Penicillins may reduce the excretion of methotrexate, causing a potential increase in toxicity.

Mycophenolate mofetil: In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) of approximately 50% has been reported following commencement of oral amoxycillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

Renal Impairment

In patients with renal impairment, the dose should be adjusted according to the degree of impairment. Please refer DOSAGE AND ADMINISTRATION.

Hepatic Impairment

Amoxycillin/clavulanic acid should be used with caution in patients with evidence of hepatic impairment. Please refer DOSAGE AND ADMINISTRATION.

Pregnancy

Reproduction studies in animals with orally and parentrally administered amoxycillin/clavulanic acid have shown no teratogenic effects. In a single study in women with preterm, premature rupture of the foetal membrane, it was reported that prophylactic treatment with amoxycillin/clavulanic acid may be associated with an increased risk of necrotizing enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy unless considered essential by the physician.  This drug should be used during pregnancy only if clearly needed.

Lactation

Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breastfed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breastfed infant, such that breastfeeding might have to be discontinued.  With the exception of the risk of sensitization, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the infant. Amoxycillin/clavulanic acid may be used during breastfeeding after a benefit/risk assessment by the physician in charge.

Paediatric Use

Please refer

Dosage and Administration

Geriatric Use

This drug is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Undesirable Effects

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.

The ADRs derived from clinical studies and post-marketing surveillance with amoxycillin/clavulanic acid, sorted by MedDRA System Organ Class are listed below.

The following terminologies have been used in order to classify the occurrence of undesirable effects.

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

Infections and Infestations

Mucocutaneous candidosis

Common

Overgrowth of non-susceptible organisms

Not known

Blood and Lymphatic System Disorders

Reversible leucopenia (including neutropenia)

Rare

Thrombocytopenia

Rare

Reversible agranulocytosis

Not known

Haemolytic anaemia

Not known

Prolongation of bleeding time and

prothrombin time

Not known

Immune System Disorders

Angioneurotic oedema

Not known

Anaphylaxis

Not known

Serum sickness-like syndrome

Not known

Hypersensitivity vasculitis

Not known

Nervous System Disorders

Dizziness

Uncommon

Headache

Uncommon

Convulsions

Not known

Aseptic meningitis

Not known

Vascular Disorders

Thrombophlebitis at injection site

Rare

Gastrointestinal Disorders

Diarrhoea

Common

Nausea

Uncommon

Vomiting

Uncommon

Indigestion

Uncommon

Antibiotic-associated colitis

Not known

Hepatobiliary Disorders

Rise in AST and/or ALT

Uncommon

Hepatitis

Not known

Cholestatic jaundice

Not known

Skin and Subcutaneous Tissue Disorders 

Skin rash

Uncommon

Pruritus

Uncommon

Urticaria

Uncommon

Erythema multiforme

Rare

Stevens-Johnson syndrome

Not known

Toxic epidermal necrolysis

Not known

Bullous exfoliative-dermatitis

Not known

Acute generalized exanthemous pustulosis (AGEP)

Not known

Renal and Urinary Disorders

Interstitial nephritis

Not known

Crystalluria

Not known

Overdosage

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident.

Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Amoxycillin crystalluria, in some cases leading to renal failure, has been observed. Amoxycillin has been reported to precipitate in bladder catheters after I.V. administration of large doses. A regular check of patency should be maintained.

Amoxycillin/clavulanic acid should be removed from the circulation by haemodialysis.

Gastrointestinal symptoms may be treated symptomatically, with attention to the water electrolyte balance.

Incompatibility

Amoxycillin/clavulanic acid should not be mixed with blood products, other proteinaceous fluid such as protein hydrolysates or with I.V. lipid emulsions.

If amoxycillin/clavulanic acid is prescribed concurrently with an aminoglycoside, the antibiotics should not be mixed in the syringe, I.V. fluid container or giving set because loss of activity of the aminoglycoside can occur under these conditions.

ADVENT I.V. solutions should not be mixed with infusions containing glucose, dextran or bicarbonate.

Shelf-Life

See on pack.

Storage and Handling Instructions

Before Opening: Store below 25°C.

Reconstituted Solutions: For storage at 5°C, the reconstituted solution should be added to pre-refrigerated infusion bags, which can be stored for up to 8 hours. Thereafter, the infusion should be administered immediately after reaching room temperatures. Reconstituted solutions should not be frozen.

Packaging Information

ADVENT 1.2 gm Injection…………………..Vial of 20 ml

ADVENT 600 mg Injection…………………..Vial of 10 ml

ADVENT 300 mg/150 mg Injection……….....Vial of 5 ml

Last reviewed: Aug 2017

Last updated: Aug 2017