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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Indacaterol (United States and Canada: Not available): Drug information

Indacaterol (United States and Canada: Not available): Drug information
(For additional information see "Indacaterol (United States and Canada: Not available): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Arcapta Neohaler [DSC]
Brand Names: Canada
  • Onbrez Breezhaler [DSC]
Pharmacologic Category
  • Beta2 Agonist;
  • Beta2-Adrenergic Agonist, Long-Acting
Dosing: Adult

Note: Arcapta Neohaler has been discontinued in the United States for >1 year.

Chronic obstructive pulmonary disease, maintenance

Chronic obstructive pulmonary disease, maintenance: Note: Depending on symptoms and exacerbation risk, use monotherapy long-acting bronchodilator (long-acting beta agonist or long-acting muscarinic antagonist). In patients with more symptoms (eg, Group B), use in combination with long-acting muscarinic antagonist. In addition, a short-acting bronchodilator is used for intermittent symptom relief (GOLD 2023).

Dry powder inhaler (75 mcg/capsule): Oral inhalation: Contents of 1 capsule inhaled once daily via approved inhalation device. Note: Doses >75 mcg/day have been evaluated; however, no difference in efficacy or adverse events was seen between the 75 mcg dose and higher doses (Chowdhury 2011; Geake 2015). In patients with asthma, a possible increase in exacerbations and respiratory-related deaths was noted with the 300 mcg dose (Chowdhury 2011; Ferguson 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Respiratory: Cough (post-inhalation 7% to 24%)

1% to 10%:

Central nervous system: Headache (5%)

Gastrointestinal: Nausea (2%)

Respiratory: Nasopharyngitis (5%), oropharyngeal pain (2%)

<1%, postmarketing, and/or case reports: Dizziness, hypersensitivity reaction, palpitations, paradoxical bronchospasm, pruritus, skin rash, tachycardia

Contraindications

Hypersensitivity to indacaterol or any component of the formulation; monotherapy (without use of a concomitant inhaled corticosteroid) in the treatment of asthma.

Warnings/Precautions

Concerns related to adverse effects:

• Asthma-related deaths: Monotherapy with a long-acting beta-2-agonist (LABA) is contraindicated in the treatment of asthma. The use of LABAs as monotherapy has been associated with an increased risk of severe exacerbations and asthma-related deaths (SMART 2006; Walters 2007); additional data from other clinical trials suggest risk of asthma-related hospitalization may also be increased with LABA monotherapy in pediatric and adolescent patients. However, data from large randomized, double-blind controlled trials do not show a significant increase in risk of serious asthma related events (including hospitalizations, intubations, and death) in adults, adolescents, and pediatric patients (4 to 11 years of age) when fixed-dose LABAs are used with inhaled corticosteroids combined in a single inhaler compared with inhaled corticosteroid monotherapy (FDA 2017). Indacaterol is not indicated for the treatment of asthma.

• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; this reaction should be distinguished from inadequate response. Discontinue immediately if paradoxical bronchospasm occurs and institute alternative therapy.

• Hypersensitivity: Immediate hypersensitivity reactions (difficulty in breathing or swallowing; swelling of tongue, lips, and face; urticaria; skin rash) have been reported; discontinue therapy immediately if patient develops an allergic reaction.

• Serious effects/fatalities: Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension); beta-agonists may cause elevation in blood pressure and heart rate. Beta-2-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.

• Appropriate use: Do not use for acute bronchospastic episodes of chronic obstructive pulmonary disease (COPD). Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Data are not available to determine if LABA use increases the risk of death in patients with COPD. Available data do not suggest an increased risk of death with use of LABA in patients with COPD.

• Diabetes: Use with caution in patients with diabetes mellitus; beta-2-agonists may increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.

• Hyperthyroidism: Use with caution in patients with hyperthyroidism; may stimulate thyroid activity.

• Hypokalemia: Use with caution in patients with hypokalemia; beta-2-agonists may decrease serum potassium (transient).

• Seizures: Use with caution in patients with seizure disorders; beta-2-agonists may result in CNS stimulation/excitation.

Special populations:

• Pediatric: LABAs, when used as monotherapy, may increase the risk of asthma-related hospitalization in pediatric and adolescent patients. When LABAs are used in a fixed-dose combination with inhaled corticosteroids, data from large clinical trials in adolescents do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to inhaled corticosteroids alone.

Dosage form specific issues:

• Lactose: Product may contain lactose; allergic reactions possible in patients with severe milk protein allergy.

Other warnings/precautions:

• Patient information: Patients using inhaled, short-acting beta-2-agonists should be instructed to discontinue routine use of these medications prior to beginning treatment. Short-acting agents should still be provided to patients; however, use should be reserved for symptomatic relief of acute symptoms. Patients must be instructed to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use of short-acting beta-2-agonists may indicate deterioration of COPD, and medical evaluation must not be delayed.

• Tolerance/tachyphylaxis: Tolerance to the bronchodilator effect, measured by FEV1, has been observed in studies.

Product Availability

Arcapta Neohaler has been discontinued in the United States for >1 year.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Inhalation:

Arcapta Neohaler: 75 mcg [DSC] [contains lactose monohydrate, milk protein]

Generic Equivalent Available: US

No

Pricing: US

Capsules (Arcapta Neohaler Inhalation)

75 mcg (per each): $10.31

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Inhalation:

Onbrez Breezhaler: 75 mcg [DSC] [contains lactose monohydrate, milk protein]

Administration: Adult

Oral inhalation: Dry powder inhaler (capsule): Administer via oral inhalation at the same time each day using Neohaler inhaler (US labeling) or Onbrez Breezhaler (Canadian labeling) only. Do not swallow capsules. Use the new inhaler included with each prescription. Do not remove capsule from blister until immediately before use. Place one capsule into inhaler capsule chamber and close until it clicks. Pierce capsule by pressing both red buttons once on sides of device. If powder is left within capsule, repeat inhalation procedure. Do not wash mouthpiece; inhalation device should be kept dry. Discard any capsules that are exposed to air and not used immediately.

Use: Labeled Indications

Chronic obstructive pulmonary disease, maintenance: Long-term maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Metabolism/Transport Effects

Substrate of CYP2D6 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1 (minor), UGT1A1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Atomoxetine: May enhance the tachycardic effect of Beta2-Agonists. Risk C: Monitor therapy

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy

Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Risk X: Avoid combination

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination

Caffeine and Caffeine Containing Products: May enhance the adverse/toxic effect of Indacaterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Indacaterol. Risk C: Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination

Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Risk X: Avoid combination

Methacholine: Beta2-Agonists (Long-Acting) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting beta2 agonists for 36 hours before methacholine use. Risk D: Consider therapy modification

Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Theophylline Derivatives: Beta2-Agonists may enhance the adverse/toxic effect of Theophylline Derivatives. Specifically, sympathomimetic effects may be increased. Theophylline Derivatives may enhance the hypokalemic effect of Beta2-Agonists. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Beta-agonists may interfere with uterine contractility if administered during labor.

Breastfeeding Considerations

It is not known if indacaterol is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

FEV1, FVC, and/or other pulmonary function tests; serum potassium, serum glucose; blood pressure, heart rate; CNS stimulation. Monitor for increased use of short-acting beta2-agonist inhalers; may be marker of a deteriorating condition.

Mechanism of Action

Relaxes bronchial smooth muscle by selective action on beta2-receptors with little effect on heart rate; acts locally in the lung.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: 5 minutes

Peak effect: 1-4 hours

Duration: 24 hours

Absorption: Systemic: Inhalation: 43% to 45% bioavailable

Protein binding: ~95%

Metabolism: Hepatic; hydroxylated via CYP3A4, CYP2D6, and CYP1A1

Half-life elimination: 40-56 hours

Time to peak, serum: ~15 minutes

Excretion: Feces (>90%; 54% as unchanged drug [after oral administration]); urine (<2% as unchanged drug)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Onbrez;
  • (AR) Argentina: Onbrize;
  • (AT) Austria: Onbrez | Onbrez breezhaler;
  • (AU) Australia: Onbrez;
  • (BD) Bangladesh: Caterol | Dilinda unicap | Onbrez | Onriva bexicap | Oxima;
  • (BE) Belgium: Onbrez;
  • (BG) Bulgaria: Onbrez;
  • (BR) Brazil: Onbrize;
  • (CH) Switzerland: Onbrez;
  • (CO) Colombia: Onbrize | Oslif;
  • (CZ) Czech Republic: Onbrez;
  • (DE) Germany: Hirobriz Breezhaler | Onbrez | Onbrez breezhaler;
  • (DO) Dominican Republic: Onbrize;
  • (EC) Ecuador: Onbrize;
  • (EE) Estonia: Onbrez;
  • (EG) Egypt: Onbrez;
  • (ES) Spain: Hirobriz Breezhaler | Onbrez | Onbrez breezhaler | Oslif;
  • (ET) Ethiopia: Onbrez;
  • (FI) Finland: Onbrez;
  • (FR) France: Onbrez | Oslif;
  • (GB) United Kingdom: Onbrez;
  • (GR) Greece: Onbrez;
  • (HK) Hong Kong: Onbrez;
  • (HR) Croatia: Onbrez;
  • (HU) Hungary: Onbrez;
  • (ID) Indonesia: Onbrez;
  • (IE) Ireland: Onbrez;
  • (IN) India: Onbrez | Unibrez;
  • (IT) Italy: Hirobriz Breezhaler | Onbrez;
  • (JO) Jordan: Onbrez;
  • (JP) Japan: Onbrez;
  • (KR) Korea, Republic of: Onbrez;
  • (KW) Kuwait: Onbrez;
  • (LB) Lebanon: Onbrez;
  • (LT) Lithuania: Onbrez breezhaler;
  • (LU) Luxembourg: Onbrez;
  • (LV) Latvia: Onbrez;
  • (MA) Morocco: Onbrez breezhaler;
  • (MX) Mexico: Onbrize;
  • (MY) Malaysia: Onbrez;
  • (NL) Netherlands: Hirobriz | Onbrez;
  • (NO) Norway: Onbrez;
  • (NZ) New Zealand: Onbrez;
  • (PE) Peru: Onbrize;
  • (PH) Philippines: Onbrez;
  • (PK) Pakistan: Onbrez;
  • (PL) Poland: Onbrez;
  • (PR) Puerto Rico: Arcapta neohaler;
  • (PT) Portugal: Hirobriz | Onbrez | Oslif;
  • (QA) Qatar: Onbrez | Onbrez Breezhaler;
  • (RO) Romania: Onbrez;
  • (RU) Russian Federation: Onbrez | Onbrez breezhaler;
  • (SE) Sweden: Onbrez | Onbrez breezhaler;
  • (SG) Singapore: Onbrez;
  • (SI) Slovenia: Onbrez;
  • (SK) Slovakia: Onbrez;
  • (TH) Thailand: Onbrez;
  • (TN) Tunisia: Onbrez;
  • (TR) Turkey: Arcapta | Inbroxa;
  • (TW) Taiwan: Onbrez;
  • (UA) Ukraine: Onbrez;
  • (UY) Uruguay: Onbrize;
  • (VE) Venezuela, Bolivarian Republic of: Onbrize;
  • (ZA) South Africa: Onbrez
  1. Anderson JL, Adams CD, Antman EM, et al, "2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines," Circulation, 2011, 123(18):e426-579. [PubMed 21444888]
  2. Arcapta Neohaler (indacaterol) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; July 2021.
  3. Balint B, Watz H, Amos C, et al, “Onset of Action of Indacaterol in Patients With COPD: Comparison With Salbutamol and Salmeterol-Fluticasone,” Int J Chronic Obstructive Pulm Dis, 2010, 5:311-8. [PubMed 20856830]
  4. Chowdhury BA, Seymour SM, Michele TM, Durmowicz AG, Liu D, Rosebraugh CJ. The risks and benefits of indacaterol--the FDA's review. N Engl J Med. 2011;365(24):2247-2249. doi: 10.1056/NEJMp1109621. [PubMed 22168640]
  5. Dahl R, Chung KF, Buhl R, et al, “Efficacy of a New Once Daily Long-Acting Inhaled Beta2-Agonist Indacaterol versus Twice-Daily Formoterol in COPD,” Thorax, 2010, 65(6):473-9. [PubMed 20522841]
  6. European Medicines Agency , “Onbrez Breezhaler (indacaterol): EPAR Summary for the Public, 2009.” Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/001114/WC500053733.pdf
  7. Feldman G, Siler T, Prasad N, et al, “Efficacy and Safety of Indacaterol 150 mcg Once Daily in COPD: A Double-Blind, Randomised, 12-Week Study,” BMC Pulm Med, 2010, 10:11. [PubMed 20211002]
  8. Ferguson GT, Make B. Stable COPD: Initial pharmacologic management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 14, 2021.
  9. Geake JB, Dabscheck EJ, Wood-Baker R, Cates CJ. Indacaterol, a once-daily beta2-agonist, versus twice-daily beta₂-agonists or placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015;1(1):CD010139. doi:10.1002/14651858.CD010139.pub2 [PubMed 25575340]
  10. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. https://ginasthma.org/gina-reports/. 2022. Accessed September 26, 2022.
  11. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2018 Report. http://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf. Published 2018. Accessed January 12, 2018.
  12. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for prevention, diagnosis and management of COPD: 2022 report. https://goldcopd.org/2023-gold-report-2/. Updated 2023. Accessed January 30, 2023.
  13. Khindri S, Sabo R, Harris S, et al, “Cardiac Safety of Indacaterol in Healthy Subjects: A Randomized, Multidose, Placebo- and Positive-Controlled, Parallel-Group Thorough QT Study,” BMC Pulm Med, 2011, 11:31. [PubMed 21615886]
  14. Moen MD, “Indacaterol in Chronic Obstructive Pulmonary Disease,” Drugs, 2010, 70(17):2269-80. [PubMed 21080743]
  15. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM; SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129(1):15-26. [PubMed 16424409]
  16. Onbrez Breezhaler (indacaterol) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; March 2021.
  17. US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. http://www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf. Published August 28, 2007.
  18. US Food and Drug Administration (FDA). FDA Drug Safety Communication. FDA review finds no significant increase in risk of serious asthma outcomes with long-acting beta agonists (LABAs) used in combination with inhaled corticosteroids (ICS).https://www.fda.gov/Drugs/DrugSafety/ucm589587.htm?utm_campaign=Long-Acting%20Beta%20agonists%20%28LABAs%29%20and%20Inhaled%20Corticosteroids%20%28ICS%29&utm_medium=email&utm_source=Eloqua&elqTrackId=de90a40b47ac46f49cbfedb9752d9a88. Published December 2017.
  19. Walters EH, Gibson PG, Lasserson TJ, Walters JA. Long-acting beta2-agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid. Cochrane Database Syst Rev. 2007;(1):CD001385. doi:10.1002/14651858.CD001385.pub2 [PubMed 17253458]
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