1. Montelukast

2. 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)

3. 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)

4. • aa

5. Role In Asthma
• aa

6. 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

7. 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

8. • 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

9. 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)

10. Pharmacology
Absorption
• Bioavailability: 64% (mean)
• Peak plasma time: Tablet, 3-4 hr; chewable tablet, 2-2.5 hr;
granules, 1-3 hr
Distribution
• 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 B
Lactation – Unknown

11. Formulations
Oral
• Tablet (5/10mg)
• Chewable (4/5mg)
• Granules / Satchet

12. 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

13. 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

14. THANK YOU