Asthma, maintenance/controller: Note: Product selection: Individualize daily mometasone dose based on severity of symptoms, typically as follows: low doses for mild persistent asthma; low to medium doses for moderate persistent asthma; and medium to high doses for severe persistent asthma. Select a product with a favorable dosage per actuation to improve convenience and adherence (Ref).
Low to medium dose |
High dose | |
---|---|---|
a GINA 2023 | ||
Mometasone |
200 to 400 mcg/day |
>400 mcg/day |
Asmanex HFA: Metered-dose inhaler:
Patients who are not on an inhaled corticosteroid: Oral inhalation: Mometasone 100 mcg: Initial: 200 mcg twice daily; maximum dose: 800 mcg/day.
Patients currently receiving chronic oral corticosteroids: Oral inhalation: Mometasone 200 mcg: Initial: 400 mcg twice daily; maximum dose: 800 mcg/day.
Asmanex Twisthaler: Dry powder inhaler: Note: The 440 mcg daily dose may be administered in divided doses or as once daily.
Patients who previously received bronchodilators alone: Oral inhalation: Initial: 220 mcg once daily in the evening; maximum dose: 440 mcg/day.
Patients who previously received inhaled corticosteroids: Oral inhalation: Initial: 220 mcg once daily in the evening; maximum dose: 440 mcg/day.
Patients who previously received oral corticosteroids: Oral inhalation: Initial: 440 mcg twice daily; maximum dose: 880 mcg/day. Note: Prednisone should be reduced slowly (ie, no faster than 2.5 mg daily on a weekly basis), beginning after at least 1 week of mometasone therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling. However, mometasone exposure may increase with severity of hepatic impairment.
Refer to adult dosing.
(For additional information see "Mometasone (oral inhalation): Pediatric drug information")
Asthma: Note: Asmanex Twisthaler (110 mcg and 220 mcg Twisthaler) deliver 100 and 200 mcg mometasone furoate per actuation respectively; NAEPP uses doses based on delivery dose, while manufacturer recommended doses are based on inhaler amount. Maximum effects may not be evident for 1 to 2 weeks or longer; higher doses may provide additional asthma control in patients who do not respond adequately after 2 weeks of therapy. Doses should be titrated to the lowest effective dose once asthma is controlled.
Maintenance therapy:
Asmanex Twisthaler (dry powder inhaler):
Children 4 to 11 years (regardless of prior therapy): Note: Use 110 mcg inhaler: Oral inhalation (110 mcg/inhalation): Initial: 110 mcg once daily, administered in the evening. Maximum daily dose: 110 mcg/day.
Children ≥12 years and Adolescents: Dosing based on previous asthma therapy:
Patients previously treated with bronchodilators alone or with inhaled corticosteroids: Oral inhalation (220 mcg/inhalation): Initial: 220 mcg once daily, administered in the evening; may increase dose after 2 weeks if adequate response not obtained. Maximum daily dose: 440 mcg/day; may be administered as 1 inhalation twice daily or 2 inhalations once daily in the evening.
Patients previously treated with oral corticosteroids: Oral inhalation (220 mcg/inhalation): Initial: 440 mcg twice daily. Maximum daily dose: 880 mcg/day.
Asmanex HFA:
Children 5 to <12 years: Oral inhalation (50 mcg/inhalation): 100 mcg twice daily; maximum daily dose: 200 mcg/day.
Children ≥12 years and Adolescents: Note: Dosing based on previous asthma therapy:
Patients previously treated with inhaled medium dose corticosteroid: Oral inhalation (100 mcg/inhalation): 200 mcg twice daily; maximum daily dose: 800 mcg/day.
Patients previously treated with high-dose inhaled corticosteroids or oral corticosteroids: Oral inhalation (200 mcg/inhalation): 400 mcg twice daily; maximum daily dose: 800 mcg/day.
Asthma guidelines:
Global Initiative for Asthma Guidelines (Ref): Dry powder inhaler (refers to Asmanex Twisthaler 110 mcg and 220 mcg strengths):
Children 6 to 11 years: Oral inhalation:
“Low” dose: 110 mcg/day.
“Medium” dose: ≥220 to <440 mcg/day.
“High” dose: ≥440 mcg/day.
Children ≥12 years and Adolescents: Oral inhalation:
“Low” dose: 110 to 220 mcg/day.
“Medium” dose: >220 to 440 mcg/day.
“High” dose: >440 mcg/day.
National Asthma Education and Prevention Program (Ref): Dry powder inhaler (refers to Asmanex Twisthaler 220 mcg strength): Children ≥12 years and Adolescents: Oral inhalation:
"Low" dose: 200 mcg/day.
"Medium" dose: 400 mcg/day.
"High" dose: >400 mcg/day.
Mild flare, exacerbation: Limited data available:
Children ≥12 years and Adolescents with mild to moderate asthma, no prior history of life-threatening asthma exacerbations, and with good self-management skills:
It is recommended to temporarily quadruple the inhaled corticosteroid dose early in the course of a mild flare to decrease the severity of an asthma exacerbation. After symptoms stabilize or after a maximum of 14 days of quadrupled dose, whichever occurs first, patients should be returned to their baseline dose (Ref). Quadrupling the inhaled corticosteroid dose has been shown to decrease the severity of an asthma exacerbation in select patients. In a randomized trial of adolescents ≥16 years and adults (n=1,871), temporarily quadrupling the inhaled corticosteroid dose when asthma control began to deteriorate resulted in fewer severe asthma exacerbations (ie, less treatment with systemic glucocorticoids or unscheduled appointments for asthma) compared to patients who maintained their inhaled corticosteroid dose (Ref). No data for quadrupling the dose in patients <16 years of age has been published. Quintupling the dose of inhaled corticosteroids (fluticasone) in children 5 to 11 years of age was not shown to reduce the rate of severe exacerbations and may have been associated with adverse effects (decreased linear growth, particularly in patients <8 years of age) (Ref).
Conversion from oral systemic corticosteroids to orally-inhaled corticosteroids: When using mometasone oral inhalation to help reduce or discontinue oral corticosteroid therapy, begin prednisone taper after at least 1 week of mometasone inhalation therapy; prednisone should be tapered slowly (ie, no faster than 2.5 mg/day on a weekly basis); monitor patients for signs of asthma instability and adrenal insufficiency; decrease mometasone to lowest effective dose after prednisone reduction is complete.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, mometasone exposure may increase with severity of hepatic impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (3% to 22%), fatigue (1% to 13%), depression (11%)
Gastrointestinal: Oral candidiasis (≤22%)
Neuromuscular & skeletal: Musculoskeletal pain (8% to 22%), arthralgia (13%)
Respiratory: Sinusitis (3% to 22%), allergic rhinitis (adolescents & adults 14% to 20%; children 4%), upper respiratory tract infection (8% to 15%), pharyngitis (8% to 13%)
1% to 10%:
Central nervous system: Pain (1% to <3%)
Gastrointestinal: Abdominal pain (3% to 6%), dyspepsia (5%), nausea (3%), vomiting (1% to ≤3%), anorexia (1% to <3%), gastroenteritis (1% to <3%)
Genitourinary: Dysmenorrhea (9%), urinary tract infection (children 2%)
Hematologic & oncologic: Bruise (children 2%)
Infection: Influenza (4%), infection (1% to <3%)
Neuromuscular & skeletal: Back pain (6%), myalgia (3%)
Ophthalmic: Increased intraocular pressure (3%)
Otic: Otalgia (1% to <3%)
Respiratory: Paranasal sinus congestion (9%), nasopharyngitis (5% to 8%), bronchitis (3%), dry throat (1% to <3%), epistaxis (1% to <3%), flu-like symptoms (1% to <3%), nasal discomfort (1% to <3%), voice disorder (1% to <3%)
Miscellaneous: Fever (children 7%)
Postmarketing and/or case reports: Anaphylaxis, angioedema, blurred vision, bronchospasm, cataract, cough, dyspnea, exacerbation of asthma, glaucoma, growth retardation, hypersensitivity reaction, pruritus, skin rash, wheezing
Hypersensitivity to mometasone or any component of the formulation; hypersensitivity to milk proteins (Asmanex Twisthaler only); primary treatment of status asthmaticus or other acute episodes of asthma for which intensive measures are required
Canadian labeling: Additional contraindications (not in US labeling): Untreated systemic fungal, bacterial, viral, or parasitic infections; tuberculosis (TB) disease (active TB) or infection (latent TB) of the respiratory tract; ocular herpes simplex.
Concerns related to adverse effects:
• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections (particularly gastroenteritis), or other conditions with severe electrolyte loss. Select surgical patients on long-term, high-dose, inhaled corticosteroids should be given stress doses of hydrocortisone intravenously during the surgical period and the dose reduced rapidly within 24 hours after surgery (NAEPP 2007).
• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; reaction should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue mometasone and institute alternative therapy.
• Hypersensitivity: Hypersensitivity reactions (eg, allergic dermatitis, anaphylaxis, angioedema, bronchospasm, flushing, pruritus, rash, urticaria) may occur; discontinue use if reaction occurs.
• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use if possible in patients with ocular herpes; respiratory tuberculosis (TB) disease (active TB) or infection (latent TB); or untreated viral, fungal, or bacterial or parasitic systemic infections. Exposure to chickenpox or measles should be avoided; if the patient is exposed, prophylaxis with varicella zoster immune globulin or pooled intravenous immunoglobulin, respectively, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
• Oral candidiasis: Local oropharyngeal Candida infections have been reported; if this occurs, treat appropriately while continuing therapy. Patients should be instructed to rinse mouth with water (without swallowing) and spit after each use.
Disease-related concerns:
• Asthma: Appropriate use: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Use is contraindicated in status asthmaticus or during other acute asthma episodes requiring intensive measures.
• Bone mineral density: Use with caution in patients with major risk factors for decreased bone mineral count such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (eg, antiseizure medication, oral corticosteroids); long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.
• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; blurred vision, increased intraocular pressure, glaucoma, and cataracts have occurred with prolonged use. Consider routine eye exams in long-term users.
Special populations:
• Pediatrics: Orally inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients (~1 cm per year [range: 0.3 to 1.8 cm per year] and related to dose and duration of exposure). To minimize the systemic effects of orally inhaled corticosteroids, each patient should be titrated to the lowest effective dose. Growth should be routinely monitored in pediatric patients.
Dosage form specific issues:
• Lactose: Asmanex Twisthaler: May contain lactose; very rare anaphylactic reactions have been reported in patients with milk protein allergy.
Other warnings/precautions:
• Discontinuation of systemic corticosteroid therapy: A gradual tapering of dose may be required prior to discontinuing therapy; there have been reports of systemic corticosteroid withdrawal symptoms (eg, joint/muscle pain, lassitude, depression) when withdrawing oral inhalation therapy.
• Transfer to oral inhaler: When transferring to oral inhalation therapy from systemic corticosteroid therapy, previously suppressed allergic conditions (rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions) may be unmasked. Withdraw systemic corticosteroid therapy by gradually tapering the dose. Monitor lung function, beta-agonist use, asthma symptoms, and for signs and symptoms of adrenal insufficiency (eg, fatigue, lassitude, weakness, nausea/vomiting, hypotension) during withdrawal.
Although recommended in children ≥12 years and adolescents, using higher doses (quintupled) in children <12 years of age has not shown efficacy and may be associated with a higher risk of adverse effects. A study in children 5 to 11 years of age with mild to moderate persistent asthma evaluated quintupling the dose of the inhaled corticosteroid (fluticasone) following the early signs of decreased asthma control; results showed that quintupled fluticasone dosages did not reduce the rate of severe exacerbations and may have been associated with adverse effects (decreased linear growth, particularly in patients <8 years of age) (Jackson 2018).
Asmanex HFA inhaler delivers 120 actuations.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Aerosol, Inhalation, as furoate:
Asmanex HFA: 50 mcg/actuation (13 g); 100 mcg/actuation (13 g); 200 mcg/actuation (13 g)
Aerosol Powder Breath Activated, Inhalation, as furoate:
Asmanex (120 Metered Doses): 220 mcg/actuation (1 ea) [contains lactose, milk protein]
Asmanex (120 Metered Doses): 220 mcg/actuation (1 ea [DSC]) [contains milk protein]
Asmanex (14 Metered Doses): 220 mcg/actuation (1 ea) [contains lactose, milk protein]
Asmanex (14 Metered Doses): 220 mcg/actuation (1 ea [DSC]) [contains milk protein]
Asmanex (30 Metered Doses): 110 mcg/actuation (1 ea) [contains lactose, milk protein]
Asmanex (30 Metered Doses): 110 mcg/actuation (1 ea [DSC]) [contains milk protein]
Asmanex (30 Metered Doses): 220 mcg/actuation (1 ea) [contains lactose, milk protein]
Asmanex (30 Metered Doses): 220 mcg/actuation (1 ea [DSC]) [contains milk protein]
Asmanex (60 Metered Doses): 220 mcg/actuation (1 ea) [contains lactose, milk protein]
Asmanex (60 Metered Doses): 220 mcg/actuation (1 ea [DSC]) [contains milk protein]
Asmanex (7 Metered Doses): 110 mcg/actuation (1 ea [DSC]) [contains lactose, milk protein]
No
Aerosol (Asmanex HFA Inhalation)
50 mcg/ACT (per gram): $8.59
100 mcg/ACT (per gram): $9.26
200 mcg/ACT (per gram): $10.89
Aerosol powder (Asmanex (120 Metered Doses) Inhalation)
220 mcg/ACT (per each): $202.73
Aerosol powder (Asmanex (14 Metered Doses) Inhalation)
220 mcg/ACT (per each): $46.56
Aerosol powder (Asmanex (30 Metered Doses) Inhalation)
110 mcg/ACT (per each): $111.65
220 mcg/ACT (per each): $120.56
Aerosol powder (Asmanex (60 Metered Doses) Inhalation)
220 mcg/ACT (per each): $141.48
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol Powder Breath Activated, Inhalation:
Asmanex Twisthaler: 100 mcg/actuation (1 ea); 200 mcg/actuation (1 ea); 400 mcg/actuation (1 ea) [contains lactose]
Asmanex HFA: Metered-dose inhaler: Shake well prior to each inhalation. Administer as 2 inhalations twice daily (morning and evening). Prime before first use and when the inhaler has not been used for >5 days by releasing 4 test sprays into the air, away from the face, shaking well before each spray. Rinse mouth with water (without swallowing) and spit after each use. Clean mouthpiece with a dry wipe after every 7 days of use.
Asmanex Twisthaler: Dry-powder inhaler: When administered once daily, administer only in the evening. Exhale fully, then place mouthpiece in mouth holding it in a horizontal position and inhale quickly and deeply. Remove inhaler and hold breath for 10 seconds if possible. Do not breathe out through the inhaler. Rinse mouth after use.
Oral inhalation:
Asmanex Twisthaler (Dry powder inhaler): Remove inhaler from foil pouch; write date on cap label. Keep inhaler upright while removing cap, twisting in a counterclockwise direction; lifting the cap loads the device with the medication. Exhale fully prior to bringing the inhaler up to the mouth. Place inhaler in mouth, while holding it in a horizontal position. Close lips around the mouthpiece and inhale quickly and deeply. Remove the inhaler from your mouth and hold your breath for about 10 seconds, if possible. Do not exhale into inhaler. Wipe the mouthpiece dry and replace the cap immediately after each inhalation; rotate fully until click is heard. Rinse mouth with water (without swallowing) after inhalation to decrease chance of oral candidiasis. Avoid contact of the inhaler with any liquids; do not wash; wipe with dry cloth or tissue if needed. Discard the inhaler 45 days after opening foil pouch or when dose counter reads "00."
Asmanex HFA (Metered dose inhaler): Shake well prior to use; administer as 2 inhalations twice daily (morning and evening). Prime the inhaler before first use by releasing 4 test sprays into the air, away from the face, shaking well before each spray. If the inhaler has not been used for more than 5 days, prime the inhaler again with 4 test sprays. Rinse mouth with water without swallowing (decreases the chance of oral candidiasis). Do not wash inhaler with water; clean mouthpiece using a dry cloth every 7 days and discard inhaler after the counter reaches “0”.
Asthma, maintenance/controller: Maintenance treatment of asthma as prophylactic therapy in patients ≥4 years of age (Asmanex Twisthaler) and ≥5 years of age (Asmanex HFA).
Limitations of use: Not indicated for the relief of acute bronchospasm.
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Cosyntropin: Corticosteroids (Orally Inhaled) may diminish the diagnostic effect of Cosyntropin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Mometasone (Oral Inhalation). Risk C: Monitor therapy
Desmopressin: Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin. Risk X: Avoid combination
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
Tobacco (Smoked): May diminish the therapeutic effect of Corticosteroids (Orally Inhaled). Risk C: Monitor therapy
Uncontrolled asthma may negatively affect fertility by increasing time to pregnancy and reducing birth rate. Fertility may be improved in patients adequately treated with inhaled corticosteroids (Couillard 2021; ERS/TSANZ [Middleton 2020]). Inhaled corticosteroids used for the treatment of asthma should not be discontinued in patients planning to become pregnant (GINA 2023). The lowest dose that maintains asthma control should be continued (ERS/TSANZ [Middleton 2020]).
Maternal use of inhaled corticosteroids (ICS) in usual doses is not associated with an increased risk of fetal malformations; a small risk of malformations was observed in one study following high maternal doses of an alternative inhaled corticosteroid (ERS/TSANZ [Middleton 2020]).
Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low-birth-weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes) (ERS/TSANZ [Middleton 2020]; GINA 2023).
Inhaled corticosteroids are recommended for the treatment of asthma during pregnancy. Due to the risk of exacerbations, stepping down or stopping ICS should not be done during pregnancy (GINA 2023). Mometasone oral inhalation is considered probably acceptable for use during pregnancy. Pregnant patients adequately controlled on mometasone for asthma may continue therapy; if initiating treatment during pregnancy, use of an agent with more data in pregnant patients may be preferred. The lowest dose that maintains asthma control should be used. Maternal asthma symptoms should be monitored monthly during pregnancy (ERS/TSANZ [Middleton 2020]; GINA 2023).
Data collection to monitor pregnancy and infant outcomes associated with asthma and the medications used to treat asthma in pregnancy is ongoing. Health care providers are encouraged to enroll exposed pregnant patients in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS) (877-311-8972 or http://mothertobaby.org). Patients may also enroll themselves.
It is not known if mometasone is present in breast milk following oral inhalation; however, oral absorption is limited (<1%). Systemic corticosteroids are 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.
Mometasone oral inhalation is considered probably acceptable with breastfeeding (ERS/TSANZ [Middleton 2020]).
Asmanex Twisthaler may contain lactose.
FEV1, peak flow, and/or other pulmonary function tests; bone mineral density; growth (adolescents and children via stadiometry); signs/symptoms of HPA axis suppression/adrenal insufficiency; possible eosinophilic conditions (including eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]); signs/symptoms of oral candidiasis; asthma symptoms; glaucoma/cataracts
May depress the formation, release, and activity of endogenous chemical mediators of inflammation (kinins, histamine, liposomal enzymes, prostaglandins). Leukocytes and macrophages may have to be present for the initiation of responses mediated by the above substances. Inhibits the margination and subsequent cell migration to the area of injury, and also reverses the dilatation and increased vessel permeability in the area resulting in decreased access of cells to the sites of injury.
Onset of action: Maximum effects may not be evident for ≥1 to 2 weeks
Duration after discontinuation: Several days or more
Absorption: <1%; clinical effects are due to direct local effect, rather than systemic absorption
Distribution: Vd: 152 L
Protein binding: 98% to 99%
Metabolism: Extensive in the liver to multiple metabolites; no major metabolites are detectable in the plasma; in vitro incubation studies identified one minor metabolite, 6 Beta-hydroxymometasone furoate, formed via cytochrome P450 CYP3A4 pathway
Bioavailability: Single dose: <1%
Half-life elimination: Mean: 5 hours
Time to peak, plasma: 0.5 to 2.5 hours
Excretion: Feces (~74%), urine (~8%)
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