ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Zileuton: Drug information

Zileuton: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Zileuton: Patient drug information" and "Zileuton: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Zyflo
Pharmacologic Category
  • 5-Lipoxygenase Inhibitor
Dosing: Adult
Asthma

Asthma:

Immediate release: Oral: 600 mg 4 times daily

Extended release: Oral: 1,200 mg twice daily

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Use is contraindicated in patients with active liver disease or persistent transaminase elevations ≥3 times the upper limit of normal.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Zileuton: Pediatric drug information")

Asthma

Asthma: Note: Current guidelines do not describe a role for zileuton in the management of asthma (Ref); not routinely used. Children ≥12 years and Adolescents:

Immediate release: Oral: 600 mg 4 times daily; maximum daily dose: 2,400 mg/day

Extended release: Oral: 1,200 mg twice daily; maximum daily dose: 2,400 mg/day

Dosing: Kidney Impairment: Pediatric

No dosage adjustment necessary in renal impairment or with hemodialysis; dialysis: <0.5% removed by hemodialysis.

Dosing: Hepatic Impairment: Pediatric

Contraindicated in patients with active liver disease or persistent transaminase elevations ≥3 times the upper limit of normal.

Adverse Reactions

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

>10%: Central nervous system: Headache (23% to 25%)

1% to 10%:

Cardiovascular: Chest pain

Central nervous system: Pain (8%), dizziness, drowsiness, hypertonia, insomnia, malaise, nervousness

Dermatologic: Pruritus, skin rash

Gastrointestinal: Dyspepsia (8%), nausea (5% to 6%), abdominal pain (5%), diarrhea (5%), constipation, flatulence, vomiting

Genitourinary: Urinary tract infection, vaginitis

Hematologic & oncologic: Leukopenia (1% to 3%), lymphadenopathy

Hepatic: Increased serum ALT (≥3 x ULN: 2% to 5%), hepatotoxicity

Hypersensitivity: Hypersensitivity reaction

Neuromuscular & skeletal: Myalgia (7%), weakness (4%), arthralgia, neck pain, neck stiffness

Ophthalmic: Conjunctivitis

Respiratory: Upper respiratory tract infection (9%), sinusitis (7%), pharyngolaryngeal pain (5%)

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Behavioral changes, hepatic failure, hepatitis, hyperbilirubinemia, jaundice, mood changes, sleep disorder, suicidal tendencies, urticaria

Contraindications

Hypersensitivity to zileuton or any component of the formulation; active liver disease or transaminase elevations ≥3 times ULN

Warnings/Precautions

Concerns related to adverse effects:

• Hepatotoxicity: There have been reports of hepatic adverse effects (elevated transaminase levels); serum ALT should be monitored. Females >65 years and patients with pre-existing elevated transaminases may be at greater risk. Discontinue therapy and follow transaminases until normal if patients develop clinical signs/symptoms of liver dysfunction or with transaminase levels >5 times ULN; use caution with history of liver disease and/or in those patients who consume substantial quantities of ethanol.

• Neuropsychiatric events: Postmarketing reports of behavioral changes and sleep disorders have been noted.

Concurrent drug therapy issues:

• Sedatives: CNS effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Older adult: Females >65 years of age may be at increased risk for ALT elevations. Pharmacokinetics were similar in older adults (≥65 years) compared to younger adults.

• Pediatric: Due to the risk of hepatotoxicity, the manufacturer does not recommend use of zileuton in children <12 years of age.

Other warnings/precautions:

• Reversal of bronchospasm: Not indicated for the reversal of bronchospasm in acute asthma attacks, including status asthmaticus; therapy may be continued during acute asthma exacerbations.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Zyflo: 600 mg [scored]

Tablet Extended Release 12 Hour, Oral:

Generic: 600 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Tablet, 12-hour (Zileuton ER Oral)

600 mg (per each): $32.22

Tablets (Zyflo Oral)

600 mg (per each): $37.59

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.

Administration: Adult

Immediate release: Administer without regard to meals.

Extended release: Swallow tablet whole; do not crush, cut, or chew; administer within 1 hour after morning and evening meals.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR tablet formulation is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.

Administration: Pediatric

Oral:

Immediate release: May administer daily doses at meals and bedtime.

Extended release: Do not crush, cut, or chew tablet; administer within 1 hour after morning and evening meals. If dose is missed, it does not need administered; at the next scheduled time administer the next dose; do not double the dose.

Use: Labeled Indications

Asthma: Prophylaxis and chronic treatment of asthma in adults and children ≥12 years of age

Limitations of use: Not indicated for relief of acute bronchospasm

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak)

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 drug interactions program by clicking on the “Launch drug interactions program” link above.

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination

Lomitapide: Zileuton may increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent zileuton; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk D: Consider therapy modification

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

Propranolol: Zileuton may increase the serum concentration of Propranolol. Risk C: Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

Warfarin: Zileuton may increase the serum concentration of Warfarin. Risk C: Monitor therapy

Food Interactions

Zyflo CR: Improved absorption when administered with food. Management: Administer with food.

Pregnancy Considerations

Uncontrolled asthma is associated with adverse events in 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). Maternal asthma symptoms should be monitored monthly during pregnancy. Agents other than zileuton are preferred for the treatment of asthma during pregnancy (ERS/TSANZ [Middleton 2020]; GINA 2021).

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 (877-311-8972 or https://mothertobaby.org). Patients may also enroll themselves.

Breastfeeding Considerations

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

According to the manufacturer, due to the potential tumorigenicity of zileuton in animal studies, 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.

Dietary Considerations

Immediate release: Take without regard to meals.

Extended release: Take with food.

Monitoring Parameters

Hepatic transaminases (prior to initiation and during therapy), specifically monitor serum ALT (prior to initiation, once-a-month for the first 3 months, every 2 to 3 months for the remainder of the first year, and periodically thereafter for patients receiving long-term therapy)

Mechanism of Action

Specific 5-lipoxygenase inhibitor which inhibits leukotriene formation. Leukotrienes augment neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction (which contribute to inflammation, edema, mucous secretion, and bronchoconstriction in the airway of the asthmatic).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Well-absorbed

Distribution: 1.2 L/kg

Protein binding: 93%, primarily albumin

Metabolism: Hepatic and gastrointestinal; zileuton and N-dehydroxylated metabolite can be metabolized by CYP1A2, 2C9, and 3A4

Half-life elimination: ~3 hours

Time to peak: Immediate release: 1.7 hours

Excretion: Urine (~95% primarily as metabolites); feces (~2%)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: The mean apparent plasma clearance of zileuton in subjects with hepatic impairment was approximately half the value of the healthy subjects. The percent binding of zileuton to plasma proteins after multiple dosing was significantly reduced in patients with moderate hepatic impairment.

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

  • (FR) France: Zyflo;
  • (PR) Puerto Rico: Zileuton extended release | Zyflo
  1. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention (2018 update). http://www.ginasthma.org. Updated 2018. Accessed January 10, 2019.
  2. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf. Updated 2020. Accessed May 6, 2020.
  3. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf. Updated 2021. Accessed May 28, 2021.
  4. Middleton PG, Gade EJ, Aguilera C, et al. ERS/TSANZ task force statement on the management of reproduction and pregnancy in women with airways diseases. Eur Respir J. 2020;55(2):1901208. doi:10.1183/13993003.01208-2019 [PubMed 31699837]
  5. National Asthma Education and Prevention Program (NAEPP). Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma. Clinical Practice Guidelines, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 08-4051. Published August 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
  6. Zileuton extended-release tablets [prescribing information]. Upper Saddle River, NJ: DASH Pharmaceuticals LLC; November 2020.
  7. Zyflo (zileuton) [prescribing information]. Cary, NC: Chiesi USA, Inc; January 2017.
  8. Zyflo CR (zileuton) [prescribing information]. Cary, NC: Chiesi USA, Inc; March 2019.
Topic 10054 Version 205.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟