montelukast by aseem
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Montelukast
Introduction
• MK-0476 ; Singulair (US) Montair (IN) Lukotas (IN) Monteflo (EU)
C35H35ClNNaO3S
• Developed by Merck in Montreal
• Developed as a maintenance therapy for Asthma / Seasonal Allergies
• Leukotriene Receptor Antagonist (LTRA)
Mechanism of Action
• Blocks LTD4 action on Cys-LT1 receptors on Bronchi / Mast Cells / Eosinophils / Basophils
• LT = ‘Slow Eicosanoid mediators of inflammation’ ; renamed as Leukotriene Modifiers
• Others-in-Class Zafirlukast (Acculate) / Pranlukast (Ultair)
• 5-LOX-Inhibitors Zileuton (Zyflo)
• aa
Role In Asthma
• aa
Indications
FDA-Approved• Prophylaxis of Chronic Asthma• Exercise-Induced Bronchoconstriction (EIB)
Off-label uses• Allergic Rhinitis• Chronic Urticaria• COPD• Atopic Dermatitis• Migraine Prophylaxis• Sinonasal polyposis
Studies i/v/o CIU• Berkun and Shalit reported a case of successfully treated steroid-
dependent delayed pressure urticaria with montelukast
• Ellis reported 2 cases successfully treated with zileuton
• Norris and Sullivan reported 9 of 15 steroid-requiring patients achieved control with zafirlukast
• Chiu and Warren noted 8 of 15 subjects responded to zafirlukast
• Spector and Tan noted one case controlled by zafirlukast and the other by zileuton
• No RCTs published concerning treating chronic urticaria with leukotriene modifiers
• Bensch and Borish performed a retrospective chart review and identified 18 patients with chronic urticaria treated with leukotriene inhibitors
• Ten had “dramatic” improvement– four with montelukast– five with zafirlukast– one with both zafirlukast and zileuton
• Improvement seen within 1 week; resolution of urticaria within one month
• ??? Better response to LOX-I > LTRA
Studies i/v/o AD
• As of 2000, only two published papers address this issue
• Carucci et al. reported a series of 4 cases using zafirlukast with observed subjective improvement
• A pilot study using Montelukast recently concluded• • Woodmansee and Simon- Atopic Dermatitis Pilot
Study using Zileuton on 14 pts (05 improved)
Pharmacology
Absorption• Bioavailability: 64% (mean)• Peak plasma time: Tablet, 3-4 hr; chewable tablet, 2-2.5 hr; granules,
1-3 hrDistribution• Protein bound: >99%Metabolism• Metabolized by CYP3A4 and CYP2C9 Elimination• Half-life: 2.7-5.5 hr• Excretion: Feces (86%), urine (0.2%)
Pregnancy Cat BLactation – Unknown
Formulations
Oral • Tablet (5/10mg) • Chewable (4/5mg) • Granules / Satchet
Dosage• > 15 yrs : 10 mg PO od
• 6 -14 yrs: 5mg PO od (Chewable)
• 2 - 5 yrs: 4mg chewable tablet / one packet of 4mg oral granules PO qd
• 12- 23 mo : One satchet 4mg PO qd
• < 12 mo : Safety-Efficacy not estabilished
• Best taken in the evening ; No regard to food
ADRs
• Headache (18.4%)• Abdominal pain (≥2%) Gastroenteritis (2%)• Laryngitis (≥2%) Pharyngitis (≥2%)• Dizziness (2%)• Elevated liver function tests (2%)• Urticaria (2%) Eczema (≥1%)• Cough (≥1%) Sinusitis (≥1%)• Churg-Strauss syndrome (AEGPA); rare • Aggressive behavior, suicidal thoughts
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