Logo AVELON Tablets
AVELON IV Solution for Infusion

PMR 01143137 and PMR 01158983


(and dosage form):

AVELON Tablets
AVELON IV Solution for Infusion

Avelon film coated tablet contains
moxifloxacin hydrochloride equivalent to 400 mg moxifloxacin.
A single sterile unit of Avelon IV 250 mL infusion solution contains moxifloxacin hydrochloride equivalent to 400 mg moxifloxacin.

A. 20.1.1 Broad and medium spectrum antibiotic

Moxifloxacin is a fluoroquinolone antibacterial with a broad spectrum of bactericidal action.
Moxifloxacin has been shown to be active against most of the following microorganisms in vitro. In-vitro sensitivity may not always have been confirmed in clinical infection (see Indications).

Moxifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative microorganisms. The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination. It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety.
The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, beta-lactams, aminoglycosides, or tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to moxifloxacin and other quinolones. There is no known cross-resistance between moxifloxacin and other classes of antimicrobials.
Cross-resistance has been observed between moxifloxacin and other fluoroquinolones against Gram-negative bacteria. Gram-positive bacteria resistant to other fluoroquinolones may, however, still be susceptible to moxifloxacin.
Moxifloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
  Aerobic Gram-positive microorganisms
        Staphylococcus aureus (methicillin-susceptible strains only)
        Streptococcus pneumoniae (penicillin-susceptible strains)
  Aerobic Gram-negative microorganisms
        Haemophilus influenzae
        Haemophilus parainfluenzae
        Klebsiella pneumoniae
        Moraxella catarrhalis
  Other microorganisms
        Chlamydia pneumoniae
        Mycoplasma pneumoniae
The following in vitro data are available, but their clinical significance is unknown.
Moxifloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 2 micrograms/mL or less against most (>90%) strains of the following microorganisms, however, the safety and effectiveness of moxifloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
  Aerobic Gram-positive microorganisms
        Streptococcus pneumoniae (penicillin-resistant strains)
        Streptococcus pyogenes
  Aerobic Gram-negative microorganisms
        Citrobacter freundii
        Enterobacter cloacae
        Escherichia coli
        Klebsiella oxytoca
        Legionella pneumophila
        Proteus mirabilis
  Anaerobic microorganisms
        Fusobacterium species
        Peptostreptococcus species
        Prevotella species
Avelon tablets
Following oral administration moxifloxacin is absorbed rapidly and almost completely. The absolute bioavailability amounts to approx. 90% after oral administration of a 400 mg dose.
Pharmacokinetics are linear in the range of 50-1200 mg single oral dose and up to 600 mg once daily dosing over 10 days. Steady state is reached within 3 days. Following a 400 mg oral dose peak concentrations of 3.1 mg/L are reached within 0.5-4 h post administration. Peak and trough plasma concentrations at steady state (400 mg once daily) were 3.2 and 0.6 mg/L, respectively.
Avelon IV
After a single 400 mg intravenous 1 hour infusion, peak plasma concentrations of approximately 4.1 mg/L were observed at the end of the infusion corresponding to about 26% higher concentrations than those after oral administration (3.1 mg/L). The AUC value of approximately 39 mg.h/L after intravenous administration is only slightly higher than that observed after oral administration (35 mg.h/L) in accordance with the absolute bioavailability of approximately 91%. In patients, mean peak plasma concentrations of 4.4 mg/L were observed at steady-state.
Pharmacokinetics are linear up to 600 mg single intravenous dose and up to 600 mg once daily dosing over 10 days.
Pharmacokinetic studies with the oral tablet and intravenous solution have therefore shown the two dosage forms are bioequivalent with respect to the systemic exposure pharmacokinetic parameter AUC.
Avelon tablets and Avelon IV
Moxifloxacin is distributed to extravascular spaces. Exposure to drug in terms of AUC (AUC
norm = 6 kg*h/L) is high; the volume of distribution at steady state amounts to Vss of approx. 2 L/kg. In saliva peak concentrations and similar to those of plasma may be reached. Due to low protein binding (approx. 45%) high free peak concentrations >10 x MIC are observed. In in vitro and ex vivo experiments protein binding over a range of 0.02 to 2 mg/L resulted in a protein binding of approximately 45% independent from the concentration of the drug. Moxifloxacin is mainly bound to serum albumin.
In tissues like lung (epithelial fluid, alveolar macrophages, biotic tissue), the sinuses (maxillary and ethmoid sinus, nasal polypi) and inflamed lesions (cantharide blister fluid) concentrations exceeding those of the plasma are reached.
The following peak concentrations were observed following intravenous and oral administration of a single dose of 400 mg moxifloxacin:
Tissue Concentration (i.v.)
Site: Plasma
        ratio (i.v.)
Plasma         4.1         -
Saliva         5.0         0.82-1.37
Blister fluid         1.75(1)                1.7(1)
Interstitial fluid         1.0(2)         0.8-2.5(2,3)

Tissue Concentration (p.o.)
Site: Plasma
ratio (p.o.)
Plasma         3.1         -
Saliva         3.6         0.75-1.3
Blister fluid         1.6(1)         1.7(1)
Bronchial mucosa         5.4         1.7-2.1
Epithelial lining fluid         20.7         5-7
Interstitial fluid         1.0(2)         0.8-1.4(2,3)
(1) 10 h after administration
(2) unbound concentration
(3) from 3 h up to 36 h post dose
Moxifloxacin undergoes Phase II biotransformation and is excreted via renal and biliary/faecal pathways as unchanged drug as well as in form of a sulfo-compound (M1) and a glucuronide (M2). M1 and M2 are the only metabolites relevant in humans, both are microbiologically inactive. The recovery from urine (approx. 19% for unchanged drug, approx. 2.5% for M1, and approx. 14% for M2) and faeces (approx. 25% of unchanged drug, approx. 36% for M1, and no recovery for M2) totalled to approx. 96.98% of the dose independent from the route of administration.
Moxifloxacin is eliminated from plasma and saliva with a mean terminal half life of approximately 12 hours. The mean apparent total body clearance following a 400 mg dose ranges from 179 to 246 mL/min. Renal clearance amounted to about 24-53 mL/min suggesting partial tubular reabsorption of the drug from the kidneys. Approximately 19% of the dose is excreted unchanged into the urine and approx. 25% in the faeces. Approx. 2.5% is recovered as M1 in the urine and 36% in the faeces, respectively. About 14% is recovered as M2 in the urine.

Avelon tablets and Avelon IV solution for infusion
Avelon tablets and Avelon IV solution for infusion are indicated for the treatment of adults (> 18 years of age) with mild to moderately severe infections caused by susceptible strains of the designated microorganisms in the conditions listed below:
- Acute Bacterial Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.
- Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Staphylococcus aureus or Moraxella catarrhalis.
- Community Acquired Pneumonia (of mild to moderate severity) caused by Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae or Moraxella catarrhalis.
- Skin and soft tissue infections caused by S. aureus, S. pyogenes.
Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to moxifloxacin. Therapy with AVELON may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

Known hypersensitivity to any component of the tablets or infusion solution or other
Due to the lack of clinical data, the use of moxifloxacin is not recommended in patients with moderate or severe hepatic insufficiency.
Quinolones are known to distribute well into breast milk of lactating women. The use of moxifloxacin in pregnancy and nursing mothers is contra-indicated.
Avelon is contra-indicated in children under 18 years and in growing adolescents, (except where no other suitable antimicrobial agent can be used). Experimental evidence indicates that, species variable reversible lesions of the cartilage of weight bearing joints has been seen in immature members of certain animal species.



Pharmacokinetic studies between moxifloxacin and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. An additive effect of moxifloxacin and these drugs cannot be excluded; therefore moxifloxacin should be used with caution when given concurrently with these drugs.
The effect of moxifloxacin on patients with congenital prolongation of the QT interval has not been studied; however, it is expected that these individuals may be more susceptible to drug-induced QT prolongation. Because of limited clinical experience, moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischemia.
The magnitude of QT prolongation may increase with increasing concentrations of the drug; therefore the recommended dose should not be exceeded. QT prolongation may lead to an increased risk for ventricular arrhythmias including torsade de pointes. In patients with paired valid ECGs in Phase III clinical trials, the mean + SD effect of moxifloxacin 400 mg on the QTc interval was 6 + 26 msec. No cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin treatment in over 4000 patients; however, certain predisposing conditions may increase the risk for ventricular arrhythmias.
The oral administration of moxifloxacin caused lameness in immature dogs. Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species.
Convulsions have been reported in patients receiving quinolones. Quinolones may also cause central nervous system (CNS) events including: dizziness, confusion, tremors, hallucinations, depression, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin, the drug should be discontinued and appropriate measures instituted. As with all quinolones, moxifloxacin should be used with caution in patients with known or suspected CNS disorders (e.g. severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold. (See PRECAUTIONS: and ADVERSE REACTIONS:)
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial oedema, dyspnea, urticaria, and itching. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Moxifloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Oxygen, intravenous steroids, and airway management, including intubation, may be administered as indicated.
Severe and sometimes fatal events, some due to hypersensitivity, and some of uncertain etiology, have been reported in patients receiving therapy with all antibiotics. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following: rash, fever, eosinophilia, jaundice, and hepatic necrosis.
Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of “antibiotic-associated colitis.”
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis.
Although not observed in moxifloxacin clinical trials, Achilles and other tendon ruptures that required surgical repair or resulted in prolonged disability have been reported with quinolones. Moxifloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon.

Quinolones may cause central nervous system (CNS) events, including: nervousness, agitation, insomnia, anxiety, nightmares or paranoia. (See WARNINGS and Information for Patients.)
Information for Patients:
To assure safe and effective use of moxifloxacin, the following information and instructions should be communicated to the patient when appropriate:
Patients should be advised:
that moxifloxacin may produce changes in the electrocardiogram (QTc interval prolongation).
that moxifloxacin should be avoided in patients receiving Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic agents.
that moxifloxacin may add to the QTc prolonging effects of other drugs such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants.
to inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as recent hypokalemia, significant bradycardia, acute myocardial ischemia.
to inform their physician of any other medications when taken concurrently with moxifloxacin, including over-the-counter medications.
to contact their physician if they experience palpitations or fainting spells while taking moxifloxacin.
that moxifloxacin tablets may be taken with or without meals, and to drink fluids liberally.
that moxifloxacin may be associated with hypersensitivity reactions, even following a single dose, and to discontinue the drug at the first sign of a skin rash or other signs of an allergic reaction.
to discontinue treatment; rest and refrain from exercise; and inform their physician if they experience pain, inflammation, or rupture of a tendon.
that moxifloxacin may cause dizziness and lightheadedness; therefore, patients should know how they react to this drug before they operate a vehicle or machinery or engage in activities requiring mental alertness or coordination.
that phototoxicity has been reported in patients receiving certain quinolones. There was no phototoxicity seen with moxifloxacin at the recommended dose. In keeping with good medical practice, avoid excessive sunlight or artificial ultraviolet light (e.g. tanning beds). If sunburn-like reaction or skin eruptions occur, contact your physician. (See Photosensitivity Potential.)
that convulsions have been reported in patients receiving quinolones, and they should notify their physician before taking this drug if there is a history of this condition.
that in some instances, hypersensitivity and allergic reactions occurred after the first administration and that the doctor should be informed immediately. Anaphylactic reactions in very rare instances can progress to a life threatening shock, in some instances after the first administration. In these cases moxifloxacin has to be discontinued, and medical treatment (e.g. treatment for shock) would be required.

Avelon tablets and intravenous solution:
The recommended dose for AVELON is 400 mg once-daily for all indications.

Method of administration - Adults
The tablets are swallowed whole with a glass of water. They can be taken independent of food intake.
The infusion solution should be infused intravenously over 60 minutes. It can be administered directly or together with compatible infusion solutions. The following coinfusions were found to form stable mixtures over a period of 24 hours at room temperature with moxifloxacin infusion solution, and can therefore be considered as compatible:
Water for Injections
Sodium Chloride 0.9%
Sodium Chloride 1 molar
Glucose 5%
Glucose 10%
Glucose 40%
Ringer solution
Lactated Ringer solution
The following coinfusions were found to be incompatible with moxifloxacin infusion solution:
Sodium Chloride 10% and 20% (Precipitation can occur at higher ratios)
Sodium Bicarbonate 4.2% and 8.4% (causes pH shift, and CO
2 bubbles can form)
If Avelon infusion solution is to be given with another drug, each drug should be given separately. Only clear solutions are to be used. Do not use if the solution is cloudy.

Duration of treatment
The duration of treatment should be determined by the severity of the indication or clinical response. In general, antibiotic therapy should be used for 3-4 days after the manifestations of the infection have cleared.
The following general recommendations for the treatment of upper and lower respiratory tract infections are made:
Acute exacerbation of chronic bronchitis,         5 days
Community acquired pneumonia,         10 days
Acute sinusitis,         10 days
The recommended duration of treatment in Skin and soft tissue infections is 10 days.
Avelon 400 mg tablets have been studied in clinical trials for up to 14 days treatment.
The recommended duration of intravenous treatment is up to 14 days. Therapy may be initial intravenous administration, followed by oral tablet administration, when clinically indicated. Alternatively, moxifloxacin can be administered intravenously for the entire treatment duration.

Special Populations
No adjustment of dosage is required in the elderly.
The use of moxifloxacin in children and adolescents in the growth phase is contra-indicated.
Hepatic impairment
No dosage adjustment is required in patients with slightly impaired liver function (Child-Pugh A). No pharmacokinetic data is available for patients with moderate to severely impaired liver function (Child-Pugh B, C). Due to the lack data, AVELON is not recommended in patients with moderate or severe hepatic impairment.
Renal impairment
No dose adjustment is required in patients with any degree of renal impairment (including creatinine clearance <30 mL/min/1,73m²). There is no pharmacokinetic data available in patients on dialysis treatment, or in patients with advanced renal impairment who are not on a dialysis programme. AVELON should therefore not be used in these patients.
Interethnic differences
No adjustment of dosage is required in ethnic groups.
Dosage adjustments based on gender are not necessary.

The most common adverse drug reactions are:
Incidence of frequency >1% <10%
Body as a whole:                abdominal pain, headache, injection site reaction
(e.g. Oedema, hypersensitivity, inflammation, pain, phlebitis)
Digestive system: nausea, diarrhoea, vomiting, dyspepsia abnormal liver function test
Special senses: taste perversion
Nervous system: dizziness
Cardiovascular system: QT prolongation in patients with concomitant hypokalemia
Incidence of frequency >0.1% <1%
Body as a whole: asthenia, moniliasis, pain, back, pain, malaise, lab test abnormal, chest pain, allergic reaction, leg pain
Cardiovascular system: tachycardia, peripheral oedema, hypertension, palpitation
Digestive system: dry mouth, nausea and vomiting, flatulence, constipation, oral moniliasis, anorexia, stomatitis, gastrointestinal disorder, glossitis, gammaGT increase
Hemic and lymphatic system: leukopenia, prothrombin decrease, eosinophilia, thrombocytemia, thrombopenia, anaemia
Musculoskeletal system: arthralgia, myalgia
Nervous system: insomnia, vertigo, nervousness, somnolence, anxiety, tremor, paresthesia, confusion, depression
Skin and appendages: rash, pruritus, sweating, urticaria
Special senses: amblyopia
Urogenital system: vaginal moniliasis, vaginitis
Incidence of frequency >0.01% <0.1%
Body as a whole: pelvic pain, face oedema, back pain, lab test abnormal, allergic reactions, leg pain
Cardiovascular system: hypotension, vasodilatation, peripheral oedema
Digestive system: gastritis, tongue discoloration, dysphagia, jaundice, diarrhoea (clostridium difficile)
Hemic and lymphatic system: thromboplastin decrease, prothrombin increase
Metabolic and nutritional: hyperglycemia, hyperlipemia, hyperuricemia, LDH increased(in connection with abnormal liver function tests)
Musculoskeletal: arthritis, tendon disorder
Nervous system: hallucinations, depersonalisation, hypertonia, incoordination, agitation, amnesia, aphasia, emotional lability, sleep disorders, speech disorders, thinking abnormal, hypesthesia, abnormal dreams, convulsion
Respiratory system: asthma, dyspnea
Skin and appendages: rash (maculapapular, purpuric, pustular)
Special senses: tinnitus, abnormal vision, taste loss, parosmia
Urogenital system: kidney function abnormal
The most common changes in laboratory parameters without regard to drug relationship and which are not listed above as ADRs were:
  increased and decreased haematocrit, increased WBC, increased and decreased RBC, decreased blood glucose, decreased haemoglobin, increased alkaline phosphatase, increased SGOT/AST, increased SGPT/ALT, increased bilirubin, increased urea, increased creatinine, increased BUN.
It is not known whether these abnormalities were caused by the medicine or the underlying condition being treated.
Incidence of frequency <0,01%
Hypersensitivity: anaphylactic reaction, shock (anaphylactic; possibly life threatening).

Food and dairy products: Absorption of moxifloxacin was not altered by food intake. Therefore, moxifloxacin can be taken independent from food intake.
Ranitidine: The concomitant administration with ranitidine did not change the absorption characteristics of moxifloxacin significantly. Absorption parameters (C
max, tmax, AUC) were very similar indicating absence of an influence of gastric pH on moxifloxacin uptake from the gastrointestinal tract.
Antacids, minerals and multi-vitamins: Concomitant ingestion of moxifloxacin together with antacids, minerals and multi-vitamins may result in impaired absorption of the drug due to formation of chelate complexes with the multi-valent cations contained in these preparations. This may lead to plasma concentrations considerably lower than desired. Hence, antacids, anti-retroviral drugs and other preparations containing magnesium, aluminium and other minerals such as iron should be administered at least 4 hours before or 2 hours after ingestion of an oral moxifloxacin dose.
Warfarin: No interaction during concomitant treatment with warfarin on prothrombin time and other coagulation parameters has been observed.
Digoxin: The pharmacokinetics of digoxin are not significantly influenced by moxifloxacin (and vice versa).
Itraconazole: The pharmacokinetics of moxifloxacin are not significantly altered by itraconazole. No dose adjustment is necessary for itraconazole when given with moxifloxacin and vice versa.
Theophylline: No influence of moxifloxacin on theophylline pharmacokinetics (and vice versa) at steady state was detected. Hence, no recommendations with respect to theophylline dosing need to be given.
Probenecid: No significant effect on apparent total body clearance and renal clearance of moxifloxacin was found in a clinical study investigating the impact of probenecid on renal excretion. Therefore, dosing adjustments need not be made when both drugs are administered concomitantly.
Antidiabetics: Concomitant administration of Avelon tablets with glibenclamide may result in a decrease of approximately 21% in the peak plasma concentrations of glibenclamide.
Oral Contraceptives: No interaction has occurred following concomitant oral administration of moxifloxacin with oral contraceptives.
Calcium supplements: No interaction has occurred following concomitant oral administration of moxifloxacin with calcium supplements.
Morphine: Parenteral administration of morphine with moxifloxacin did not reduce the oral bioavailability of moxifloxacin.
Drugs metabolized by Cytochrome P450 enzymes: In vitro studies with cytochrome P450 isoenzymes (CYP) indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, suggesting that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes (e.g. midazolam, cyclosporine, warfarin, theophylline).
Nonsteroidal anti-inflammatory drugs (NSAIDs): Although not observed with moxifloxacin in preclinical and clinical trials, the concomitant administration of a nonsteroidal anti-inflammatory drug with a quinolone may increase the risks of CNS stimulation and convulsions. (See WARNINGS.)
Charcoal: Concomitant administration of charcoal with a dose of 400 mg oral or intravenous moxifloxacin will reduce systemic availability of the drug by more than 80% or 20% respectively.

No specific countermeasures after accidental overdosage are recommended. General symptomatic therapy should be initiated. Concomitant administration of charcoal with a dose of 400 mg oral or intravenous moxifloxacin will reduce systemic availability of the drug by more than 80% or 20% respectively. The application of charcoal may be useful to prevent excessive increase of systemic exposure to moxifloxacin in cases of oral overdose.

AVELON tablets: Dull red coated oblong, convex tablet. One side is embossed “BAYER”and the other “M400”.
AVELON IV: Clear yellow solution

AVELON tablets: Blister packs of 5 and 10 tablets
AVELON IV: 250 mL Polyolefin flexibag
AVELON IV: 250 mL Colourless glass bottle for infusion

Avelon tablets:
Store below 25°C in a dry place. Store in the manufacturer's original container.
Avelon IV:
Store below 25°C. Do not store below 8°C
. At cool storage temperatures, precipitation may occur, which will re-dissolve at room temperature. It is therefore recommended not to store the infusion solution in a refrigerator. Protect from light. Keep the flexibags in the overwrap/pouch or the bottles in the outer cartons until required for use.

Avelon tablets:                                        34/20.1.1/0008
Avelon IV solution for infusion:         36/20.1.1/0052

Bayer (Pty) Ltd
Registration No. 1968/11192/07
Wrench Road, Isando, 1600

25 October 2001


Updated on this site: February 2003
Source: Pharmaceutical Industry

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