Ceftazidime Mylan

New Zealand - English - Medsafe (Medicines Safety Authority)

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Active ingredient:
Ceftazidime pentahydrate 582 mg equivalent to 500 mg ceftazidime;  ;  
Available from:
Mylan New Zealand Ltd
INN (International Name):
Ceftazidime pentahydrate 582 mg (equivalent to 500 mg ceftazidime)
Dosage:
500 mg
Pharmaceutical form:
Powder for injection
Composition:
Active: Ceftazidime pentahydrate 582 mg equivalent to 500 mg ceftazidime     Excipient: Sodium carbonate
Units in package:
Vial, Type III glass with chlorobutyl rubber (EP) (1 vial pack) (not marketed), 500 mg
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Orchid Chemicals and Pharmaceuticals Limited
Therapeutic indications:
Indicated for the treatment of single and mixed infections caused by susceptible organisms. May be used alone as first choice medicine before the results of sensitivity tests are available. May be used in combination with an aminoglycoside or most other ?- lactam antibiotics. May be used with an antibiotic against anaerobes when the presence of Bacteroides fragilis is suspected. Susceptibility to ceftazidime will vary with geography and time and local susceptibility data should be consulted where available. Indications include: Severe infections: for example: - septicaemia, bacteraemia, peritonitis, meningitis. - infections in immunosuppressed patients. - infections in patients in intensive care, e.g. infected burns. - Respiratory tract infections including lung infections in cystic fibrosis. - Ear, nose and throat infections. - Urinary tract infections. - Skin and soft tissue infections. - Gastrointestinal, biliary, and abdominal infections. - Bone and joint infections. - Infections
Product summary:
Package - Contents - Shelf Life: Vial, Type III glass with chlorobutyl rubber (EP) or bromobutyl (EP) - 1 dose units - 24 months from date of manufacture stored at or below 25°C protect from light 24 hours reconstituted stored at 2° to 8°C (Refrigerate, do not freeze)
Authorization number:
TT50-7961a
Authorization date:
2007-05-07

Page 1 of 12

NEW ZEALAND DATA SHEET

CEFTAZIDIME MYLAN

1. Product Name

Ceftazidime Mylan, 250 mg, 500 mg, 1 g & 2 g, powder for injection.

2. Qualitative and Quantitative Composition

Each vial contains 250 mg, 500 mg, 1 g or 2 g of ceftazidime (as pentahydrate).

For the full list of excipients, see section 6.1

3. Pharmaceutical Form

Ceftazidime Mylan Powder for Injection is supplied as a white or almost white, crystalline powder,

containing 116.4 mg sodium carbonate per gram of ceftazidime.

4. Clinical Particulars

4.1

Therapeutic indications

Treatment of single or multiple infections caused by susceptible organisms.

May be used alone as first choice medicine before the results of sensitivity tests are available.

May be used in combination with an aminoglycoside or most other β- lactam antibiotics.

May be used with an antibiotic against anaerobes when the presence of Bacteroides fragilis is

suspected.

Susceptibility to ceftazidime will vary with geography and time and local susceptibility data should

be consulted where available (see section 5.1).

Indications include:

Severe infections e.g.

Septicaemia, bacteraemia, peritonitis, meningitis

Infections of immunosuppressed patients

Infections in patients in intensive care, e.g. infected burns.

Respiratory tract infections including lung infections in cystic fibrosis

Ear, nose and throat infections

Urinary tract infections

Skin and soft tissue infections

Gastrointestinal, biliary and abdominal infections

Bone and joint infections

Infections associated with haemo- and peritoneal dialysis and with continuous ambulatory peritoneal

dialysis (CAPD).

Page 2 of 12

4.2

Dose and method of administration

Dose

Dosage depends upon the severity, sensitivity, site and type of infection and upon the age and renal

function of the patient.

Adults

1-6 g/day in 2 or 3 divided doses by IV or IM injection.

Urinary tract and less severe infections

- 500 mg or 1g every 12 hours.

Most infections

- 1 g every 8 hours or 2 g every 12 hours.

Very severe infections particularly in immunocompromised patients including those with

neutropenia

- 2 g every 8 or 12 hours, or 3 g every 12 hours.

Fibrocystic adults with pseudomonal lung infections

- 100-150 mg/kg/day in 3 divided doses.

- In adults with normal renal function 9 g/day has been used without ill effect.

Special populations

Infants and children (> 2 months)

30 - 100 mg/kg/day in 2 or 3 divided doses.

Doses up to 150 mg/kg/day (maximum 6 g/day) in three divided doses may be given to infected

immunocompromised or fibrocystic children or children with meningitis.

Neonates (0 - 2 months)

25 - 60 mg/kg/day in 2 divided doses.

In neonates the serum half life of ceftazidime can be 3 - 4 times greater than that measured in adults.

Elderly

In view of the reduced clearance of ceftazidime in acutely ill elderly patients, the daily dosage should

not normally exceed 3 g, especially in those over 80 years of age.

Renal impairment

Ceftazidime is excreted unchanged by the kidneys. Therefore, in patients with impaired renal

function the dosage should be reduced.

An initial loading dose of 1 g should be given. Maintenance doses should be based on creatinine

clearance as shown in Table 1:

Page 3 of 12

Table 1: Recommended maintenance doses of ceftazidime in renal insufficiency

Creatinine clearance

(mL/min)

Approx. serum creatinine

(micromol/L)

(mg/dL)

Recommended

unit

dose of

ceftazidime

(g)

Frequency of

dosing

(hourly)

> 50

< 150

( < 1.7 )

Normal dosage

50 - 31

150 - 200

( 1.7 - 2.3 )

30 - 16

200 - 350

( 2.3 - 4.0 )

15 - 6

350 - 500

( 4.0 - 5.6 )

< 5

> 500

( > 5.6 )

In patients with severe infections the unit dose should be increased by 50% or the dosing frequency

increased. In such patients the ceftazidime serum levels should be monitored and trough levels

should not exceed 40 mg/L.

In children the creatinine clearance should be adjusted for body surface area or lean body mass.

Haemodialysis

The serum half-life during haemodialysis ranges from 3 to 5 hours.

Following each haemodialysis period the maintenance dose of ceftazidime recommended in the

above table should be repeated.

Peritoneal dialysis

Ceftazidime may be used in peritoneal dialysis and continuous ambulatory peritoneal dialysis

(CAPD).

In addition to intravenous use, ceftazidime can be incorporated into the dialysis fluid (usually 125 to

250 mg for 2 litres of dialysis solution).

For patients in renal failure on continuous arteriovenous haemodialysis or high-flux haemofiltration

in intensive therapy units; 1 g daily either as a single dose or in divided doses. For low-flux

haemofiltration follow the dosage recommended under impaired renal function.

For patients on venovenous haemofiltration and venovenous haemodialysis, follow the dosage

recommendations in tables 2 and 3 below:

Table 2: Continuous venovenous haemofiltration dosage guidelines for ceftazidime

Residual renal function

(creatinine clearance in

mL/min)

Maintenance dose (mg) for a ultrafiltration rate (mL/min)

of

a

:

5

16.7

33.3

50

Maintenance dose to be administered every 12 h.

Page 4 of 12

Table 3: Ceftazidime dosage guidelines during continuous venovenous haemodialysis

Residual renal function

(creatinine clearance in mL/min)

Maintenance dose (mg) for a dialysate inflow rate of

a

:

1.0 litres/h

2.0 litres/h

Ultrafiltration rate (litres/h) Ultrafiltration rate (litres/h)

0.5

1.0

2.0

0.5

1.0

2.0

1000

1000

1000

1000

Maintenance dose to be administered every 12 h.

Method of administration

Use Ceftazidime Mylan Powder for Injection intravenously or by deep intramuscular injection.

Recommended IM injection sites are the upper outer quadrant of the gluteus maximus or lateral part

of the thigh.

Ceftazidime solutions may be given directly into the vein or introduced into the tubing of a giving set

if the patient is receiving parenteral fluids.

On the addition of Water for Injection, Ceftazidime Mylan dissolves with effervescence to produce a

clear solution for injection or infusion.

For instruction on reconstitution of the medicine before administration, see section 6.6.

4.3

Contraindications

Patients with known hypersensitivity to cephalosporin antibiotics.

Hypersensitivity to ceftazidime pentahydrate or any of the excipients (see section 6.1).

4.4

Special warnings and precautions for use

Before beginning treatment establish whether the patient has a history of hypersensitivity reactions

to ceftazidime, cephalosporins, penicillins or other medicines. Special care is indicated in patients

who have experienced an allergic reaction to penicillins or other beta-lactams. If an allergic reaction

to ceftazidime occurs, discontinue the medicine. Serious hypersensitivity reactions may require

adrenaline, hydrocortisone, antihistamine or other emergency measures.

Concurrent treatment with high doses of cephalosporins and nephrotoxic medicines such as

aminoglycosides or potent diuretics (e.g. furosemide) may adversely affect renal function. Clinical

experience has shown that this is not likely to be a problem with ceftazidime at the recommended

dose levels. There is no evidence that ceftazidime adversely affects renal function at normal

therapeutic doses.

Ceftazidime is eliminated via the kidneys, therefore the dosage should be reduced according to the

degree of renal impairment. Neurological sequelae have occasionally been reported when the dose

has not been reduced in patients with renal impairment (see section 4.2 and section 4.8).

As with other broad spectrum antibiotics, prolonged use may result in the overgrowth of non-

susceptible organisms (e.g. Candida, Enterococci) which may require interruption of treatment or

appropriate measures. Repeated evaluation of the patient's condition is essential.

Page 5 of 12

Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity

from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who

develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the

patient experiences abdominal cramps, treatment should be discontinued immediately and the

patient investigated further.

As with other extended-spectrum cephalosporins and penicillins, some initially susceptible strains of

Enterobacter spp. and Serratia spp. may develop resistance during ceftazidime therapy. When

clinically appropriate during therapy of such infections, periodic susceptibility testing should be

considered.

Each 1 g of ceftazidime contains approximately 54 mg of sodium. The sodium content must be taken

into account in patients requiring sodium restriction.

4.5

Interaction with other medicines and other forms of interaction

Concurrent use of high doses with nephrotoxic medicines may adversely affect renal function (see

section 4.4).

Chloramphenicol is antagonistic in vitro with ceftazidime and other cephalosporins. The clinical

relevance

this

finding

unknown,

concurrent

administration

ceftazidime

with

chloramphenicol is proposed, the possibility of antagonism should be considered.

In common with other antibiotics, ceftazidime may affect the gut flora, leading to lower oestrogen

reabsorption and reduced efficacy of combined oral contraceptives.

Ceftazidime does not interfere with enzyme-based tests for glycosuria but slight interference may

occur with copper reduction methods (Benedict's, Fehling's, Clinitest).

Ceftazidime does not interfere in the alkaline picrate assay for creatinine.

4.6

Fertility, pregnancy and lactation

Pregnancy

There is no experimental evidence of embryopathic or teratogenic effects, but as with all medicines,

ceftazidime should be administered with caution during the early months of pregnancy and early

infancy.

Breast-feeding

Ceftazidime is excreted in human breast milk in small quantities and should be used with caution in

breast feeding.

Fertility

No data available. For pre-clinical fertility data refer to section 5.3.

4.7

Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. However,

undesirable effects may occur (e.g. dizziness), which may influence the ability to drive and use

machines.

4.8

Undesirable effects

Data from large clinical trials (internal and published) were used to determine the frequency of very

common to uncommon undesirable effects. The frequencies assigned to all other undesirable effects

were mainly determined using post-marketing data and refer to a reporting rate rather than a true

frequency.

The following convention has been used for the classification of frequency:

Page 6 of 12

very common ≥1/10,

common ≥1/100 and <1/10,

uncommon ≥1/1000 and <1/100,

rare ≥1/10,000 and <1/1000,

very rare <1/10,000.

Infections and infestations

Uncommon: Candidiasis (including vaginitis and oral thrush).

Blood and lymphatic system disorders

Common: Eosinophilia and thrombocytosis.

Uncommon: Leucopenia, neutropenia, and thrombocytopenia.

Very rare: Lymphocytosis, haemolytic anaemia, and agranulocytosis.

Immune system disorders

Very rare: Anaphylaxis (including bronchospasm and/or hypotension).

Nervous system disorders

Uncommon: Headache and dizziness.

Very rare: Paraesthesia.

There have been reports of neurological sequelae including tremor, myoclonia, convulsions,

encephalopathy, and coma in patients with renal impairment in whom the dose of ceftazidime has

not been appropriately reduced.

Vascular disorders

Common: Phlebitis or thrombophlebitis with IV administration.

Gastrointestinal disorders

Common: Diarrhoea.

Uncommon: Nausea, vomiting, abdominal pain, and colitis.

Very rare: Bad taste.

As with other cephalosporins, colitis may be associated with Clostridium difficile and may present as

pseudomembranous colitis (see section 4.4).

Hepatobiliary disorders

Common: Transient elevations in one or more of the hepatic enzymes, ALT (SGPT), AST (SOGT),

LDH, GGT and alkaline phosphatase.

Very rare: Jaundice.

Skin and subcutaneous tissue disorders

Common: Maculopapular or urticarial rash.

Uncommon: Pruritus.

Very rare: Angioedema, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal

necrolysis.

Page 7 of 12

General disorders and administration site conditions

Common: Pain and/or inflammation after IM injection.

Uncommon: Fever.

Investigations

Common: Positive Coombs' test.

Uncommon: As with some other cephalosporins, transient elevations of blood urea, blood urea

nitrogen and/or serum creatinine have been observed.

A positive Coombs' test develops in about 5% of patients and may interfere with blood cross-

matching.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked

to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.

4.9

Overdose

Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma.

Serum levels of ceftazidime can be reduced by haemodialysis or peritoneal dialysis.

For further advice on management of overdose please contact the National Poisons Information

Centre (0800 POISON or 0800 764 766).

5. Pharmacological Properties

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Anti-bacterials for systemic use. Third-generation cephalosporins, ATC

code: J01DD02.

The prevalence of acquired resistance is geographically and time dependent and for select species

may be very high. Local information on resistance and prevalence of extended spectrum beta

lactamase (ESBLs) producing organisms is desirable, particularly when treating severe infections.

In vitro susceptibility of micro-organisms to ceftazidime

Where clinical efficacy of ceftazidime has been demonstrated in clinical trials this is indicated with

an asterisk (*).

Commonly susceptible species

Gram-positive aerobes:

Beta-hemolytic streptococci*

Staphylococcus aureus (methicillin susceptible)*

Coagulase negative staphylococcus (methicillin susceptible)

Gram-negative aerobes:

Haemophilus influenzae* including ampicillin resistant strains

Haemophilus parainfluenzae

Neisseria gonorrhoeae

Neisseria meningitidis*

Pasteurella multocida

Proteus spp.*

Page 8 of 12

Providencia spp.

Salmonella spp.

Shigella spp.

Species for which acquired resistance may be a problem

Gram-negative aerobes:

Acinetobacter spp.

Burkholderia cepacia

Citrobacter spp.*

Enterobacter spp.*

Escherichia coli*

Klebsiella spp. including K. pneumoniae*

Pseudomonas spp. including P. aeruginosa*

Serratia spp.*

Morganella morganii

Yersinia enterocolitica

Gram-positive aerobes:

Streptococcus pneumoniae*

Viridans group streptococcus

Gram-positive anaerobes:

Clostridium spp. not including C. difficile

Peptostreptococcus spp.

Propionibacterium spp.

Gram-negative anaerobes:

Fusobacterium spp.

Inherently resistant organisms

Gram-positive aerobes:

Enterococcus spp. including E. faecalis and E. faecium

Listeria spp.

Gram-negative aerobes:

Campylobacter spp.

Gram-positive anaerobes:

Clostridium difficile

Gram-negative anaerobes:

Bacteroides spp. including B. fragilis

Others:

Chlamydia spp.

Mycoplasma spp.

Legionella spp.

Page 9 of 12

5.2

Pharmacokinetic properties

Absorption

After IM administration of 500 mg and 1 g, peak levels of 18 and 37 mg/L respectively are rapidly

achieved and 5 minutes after IV bolus injection of 500 mg, 1 g or 2 g, serum levels are respectively

46, 87 and 170 mg/L.

Distribution

Therapeutically effective concentrations are still present in the serum 8 to 12 hours after either IV or

IM administration. Serum protein binding is about 10%. Concentrations in excess of the MIC for

common pathogens can be achieved in tissues such as bone, heart, bile, sputum, aqueous humour,

synovial, pleural and peritoneal fluids. Ceftazidime crosses the placenta readily, and is excreted in

the breast milk. Penetration of the intact blood-brain barrier is poor resulting in low levels of

ceftazidime in the cerebral spinal fluid (CSF) in the absence of inflammation. However, therapeutic

levels of 4 to 20 mg/L or more are achieved in the CSF when the meninges are inflamed.

Biotransformation

Ceftazidime is not metabolised in the body.

Elimination

Parenteral administration produces high and prolonged serum levels which decrease with a half-life

of about 2 hours. Ceftazidime is excreted unchanged, in active form into the urine by glomerular

filtration; approximately 80 to 90% of the dose is recovered in the urine within 24 hours. Elimination

of ceftazidime is decreased in patients with impaired renal function and the dose should be reduced

(see section 4.2). Less than 1% is excreted via the bile, which limits the amount entering the bowel.

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology,

repeat dose toxicity, genotoxicity, toxicity to reproduction. Carcinogenicity studies have not been

performed with ceftazidime.

6. Pharmaceutical Particulars

6.1

List of excipients

Sodium carbonate (anhydrous).

6.2

Incompatibilities

Ceftazidime is less stable in Sodium Bicarbonate Injection than in other IV fluids. It is not

recommended as a diluent. Ceftazidime and aminoglycosides should not be mixed in the same

giving set or syringe. Precipitation has been reported when vancomycin has been added to

ceftazidime in solution. Therefore, it would be prudent to flush giving sets and intravenous lines

between administration of these two agents.

6.3

Shelf life

2 years.

6.4

Special precautions for storage

Store vials prior to reconstitution at or below 25

C. Store in outer packaging. Protect from light. If

storage is necessary once reconstituted, store at 2 to 8°C for not more than 24 hours.

Page 10 of 12

6.5

Nature and contents of container

Individually cartoned vials of Ceftazidime Mylan Powder for Injection containing 250 mg, 500 mg or

1 g ceftazidime (as pentahydrate) for intramuscular or intravenous use.

Cartons containing 5 vials of Ceftazidime Mylan Powder for Injection containing 1 g ceftazidime (as

pentahydrate) for intramuscular or intravenous use.

Individually cartoned vials of Ceftazidime Mylan Powder for Injection containing 2 g ceftazidime (as

pentahydrate) for intravenous use.

Cartons containing 5 vials of Ceftazidime Mylan Powder for Injection containing 2 g ceftazidime (as

pentahydrate) for intravenous use.

Not all pack types and sizes may be marketed.

6.6

Special precautions for disposal and other handling

Ceftazidime is compatible with most commonly used IV fluids. However, Sodium Bicarbonate

Injection is not recommended as a diluent (see section 6.2).

All sizes of vials of Ceftazidime Mylan Powder for Injection are supplied under reduced pressure. As

the product dissolves, carbon dioxide is released and a positive pressure develops. Small bubbles

of carbon dioxide in the constituted solution may be ignored.

Instruction for reconstitution

Vial size

Amount of

diluent to be

added (mL)

Approximate

concentration

(mg/mL)

250 mg

Intramuscular

1.0 mL

Intravenous

2.5 mL

500 mg Intramuscular

1.5 mL

Intravenous

5 mL

Intramuscular

3 mL

Intravenous bolus

10 mL

Intravenous infusion

50 mL #

Intravenous bolus

10 mL

Intravenous infusion

50 mL #

# NOTE: Addition should be in two stages (see text)

Solutions range from light yellow to amber depending on concentration, diluent and storage

conditions used. Within the stated recommendations, product potency is not adversely affected by

such colour variations.

Ceftazidime at concentrations between 1 mg/mL and 40 mg/mL is compatible with:

0.9% Sodium Chloride Injection.

M/6 Sodium Lactate Injection.

Compound Sodium Lactate Injection (Hartmann's Solution).

5% Dextrose Injection.

0.225% Sodium Chloride and 5% Dextrose Injection.

0.45% Sodium Chloride and 5% Dextrose Injection.

0.9% Sodium Chloride and 5% Dextrose Injection.

0.18% Sodium Chloride and 4% Dextrose Injection.

Page 11 of 12

10% Dextrose Injection.

Dextran 40 Injection 10% in 0.9% Sodium Chloride Injection.

Dextran 40 Injection 10% in 5% Dextrose Injection.

Dextran 70 Injection 6% in 0.9% Sodium Chloride Injection.

Dextran 70 Injection 6% in 5% Dextrose Injection.

Ceftazidime at concentrations between 0.05 mg/mL and 0.25 mg/mL is compatible with Intra-

peritoneal Dialysis Fluid (Lactate).

Ceftazidime may be constituted for intramuscular use with 0.5% or 1% Lignocaine Hydrochloride

Injection.

Both components retain satisfactory potency when ceftazidime at 4 mg/mL is admixed with:

Hydrocortisone (hydrocortisone sodium phosphate) 1 mg/mL in 0.9% Sodium Chloride

Injection or 5% Dextrose Injection.

Cefuroxime (cefuroxime sodium) 3 mg/mL in 0.9% Sodium Chloride Injection.

Cloxacillin (cloxacillin sodium) 4 mg/mL in 0.9% Sodium Chloride Injection.

Heparin 10 IU/mL or 50 IU/mL in 0.9% Sodium Chloride Injection.

Potassium Chloride 10 mEq/L or 40 mEq/L in 0.9% Sodium Chloride Injection.

The contents of a 500 mg vial of Ceftazidime Mylan Powder for Injection, constituted with 1.5 mL

Water for Injections, may be added to metronidazole injection (500 mg in 100 mL) and both retain

their activity.

Preparation of solutions for IM or IV bolus injection:

1. Introduce the syringe needle through the vial closure and inject the recommended volume of

diluent.

2. Withdraw the needle and shake the vial to give a clear solution.

3. Invert the vial. With the syringe piston fully depressed insert the needle into the solution. Withdraw

the total volume of solution into the syringe ensuring that the needle remains in the solution. Small

bubbles of carbon dioxide may be disregarded.

Preparation of solutions for IV infusion from Ceftazidime Mylan Powder for Injection (mini-

bag or burette-type set):

Prepare using a total of 50 mL of compatible diluent, added in TWO stages as below:-

1 g and 2 g vials for IV infusion:-

1. Introduce the syringe needle through the vial closure and inject 10 mL of diluent for the 1 g and

2 g vials.

2. Withdraw the needle and shake the vial to give a clear solution.

3. Do not insert a gas relief needle until the product has dissolved. Insert a gas relief needle through

the vial closure to relieve the internal pressure.

4. Transfer the reconstituted solution to final delivery vehicle (e.g. mini-bag or burette-type set)

making up a total volume of at least 50 mL, and administer by intravenous infusion over 15-30

minutes.

NOTE: To preserve product sterility, it is important that the gas relief needle is not inserted through

the vial closure before the product has dissolved.

Page 12 of 12

Disposal

Any unused medicine or waste material should be disposed of in accordance with local requirements.

7. Medicines Schedule

Prescription Medicine

8. Sponsor Details

Mylan New Zealand Ltd

PO Box 11183

Ellerslie

AUCKLAND

Telephone 09-579-2792

9. Date of First Approval

09 July 2009

10. Date of Revision of the Text

23 May 2018

Sections updated

Summary of change

Reformatted to SmPC style

Information added for Water for Injection

Revised wording for contraindication

Addition of precautionary information regarding sodium

Removed cutaneous vasculitis

Inclusion

information

regarding

data

extended

spectrum

beta

lactamases (ESBLs)

Added Preclinical safety data section

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