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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