Systemic Procaterol (Meptin) as a CONTROLLER for Asthma PART 1 Good day to you doctor. Today I would like to discuss with you Procaterol (Meptin) as a controller medication for your patients with Asthma. I will be focusing on the Systemic Forms of Meptin, particularly the Tablet Format: 25mcg and 50mcg tablets.

INFLAMMATION Environmental Risk Factors Definition of Asthma Environmental Risk Factors Airway Hyperresponsiveness Airway Limitation Symptoms Triggers INFLAMMATION As you know well, doctors, asthma is defined as a chronic inflammatory disorder of the airways, characterized by inflammation, airway hyperresponsiveness, and reversible airway obstruction. In susceptible individuals, the inflammation leads to an increase in airway responsiveness to various stimuli, and causes recurrent symptoms associated with airway obstruction that is often reversible either spontaneously or with treatment. Global Strategy for Asthma Management and Prevention, 1995

Common Asthma Triggers Allergens 1 Respiratory Tract Infections Irritants (Dust, Strong Odor, etc.) Temperature Change Emotion / Stress Exercise / Physical Activity 2 3 4 5 6 The most common stimuli or asthma triggers are listed here in this slide. As an exposure of asthmatic subjects to the stimuli induces asthmatic episodes, identification and control or avoidance of these stimuli are far most important in the management of asthma, which can reduce manifestation of symptoms and may decrease airway inflammation and hyperresponsiveness in a long-term.

Philippine Consensus Report on the Diagnosis & Management of Asthma Step 2: Mild, Persistent Controller: Daily medication: - Inhaled Corticosteroids 200-500 up to 800 mcg/day or Cromolyn Sodium Alternative Controller: -Long-Acting b2 Agonist or Sustained Release Theophylline None Step 1: Mild, Intermittent Reliever: - Inhaled Short-Acting b2 Agonist as needed, not > 3x/week Alternative Reliever: - Short-Acting Oral bronchodilator (b2 Agonist or Theophyllime) - Inhaled Short-Acting b2 Agonist as needed, not > 3-4x/day Step 4: Severe, Persistent - Add Ipratropium Bromide - Inhaled Corticosteroids 800-2,000 mcg/day - Long-Acting Bronchodilator (Inhaled or Oral b2 Agonist, Sustained Release Theophylline) - Oral Long-Acting b2 Agonist + Theophylline - Oral Steroid > 7.5 mg/day, daily or alternate day Step 3: Moderate, Persistent - Add Long-Acting Bronchodilator - Low Dose Oral Steroid < 7.5 mg/day, daily or alternate day As discussed earlier, the underlying condition of asthma is inflammation. It is, therefore, important to address the inflammation in the management of asthma. In order to address these problems, the Philippine Consensus Report in the Diagnosis & Management of Asthma recommends the use of controllers, which are mainly steroids and anti-inflammatory agents as the first choice. However, once you are faced with any of the situations wherein you do not want to increase dosage of the controller given to your patients, the condition of your patients is not properly controlled by the controller given, or you do not want to use steroids even in a form of inhaler, like for your pediatric cases, the consensus recommends to use any of the oral or long-acting bronchodilators as an additional controller.

Treatment Modality for Asthma Steroids Anti-inflammatory drugs Oral/Long acting bronchodilators Anti-inflammatory effects Reduce airway hyperreactivity Sustained bronchodilation Inflammation Airway Hyperreactivity Controller Bronchoconstriction Asthmatic attack Reliever Knowing that the underlying conditions of asthma are inflammation and airway hyperresponsiveness, I hope you will agree with us that bronchodilators having the following features are more recommended as an additional controller to steroids or anti-inflammatory drugs; 1. Anti-inflammatory effect, 2. Reduces airway hyperresponsiveness, and 3. Sustained bronchodilating action. Inhaled Bronchodilators Rapid onset of action Potent bronchodilation

Site of Action of Anti-asthmatic Drugs GTP cGMP GMP Anti-cholinergic Agents Inhibition Guanylate Cyclase Bronchoconstriction Phosphodiesterase Adenylate Cyclase Bronchodilation Xanthine Derivatives b2 Stimulants Activation Inhibition ATP cAMP AMP As you know well, we have three bronchodilators available in the market now, which are beta 2 stimulants or agonists, xanthine derivatives, and anti-cholinergic agents. Our product, Procaterol, Meptin belongs to the beta 2 stimulant category. Release Inhibition Bronchoconstriction Mucous edema Mast cell Histamine, LTs Inhibition Inhibition DSCG, DCC Anti-histaminic agents Illustration Text Book of Clinical Medicine - Respiratory Medicine

Features of Meptin Syrup & Tablets as A Controller Long Duration of Bronchodilating Action Anti-inflammatory Effect Our product, Procaterol, Meptin has the following features, which meet the criteria for a bronchodilator as a controller in the management of asthmatic patients, as discussed in the previous slide; 1. Long duration of bronchodilating action, 2. Anti-inflammatory effect, and 3. Reduces airway hyperreactivity. For the course of my next visits, I will be tackling individually these three functions of Procaterol. Reduces Airway Hyperreactivity

Bronchodilating Action of Procaterol Method of Administration: Intraduodenal (%) Procaterol (n=8) 0.3μg/kg Salbutamol (n=8) 3μg/kg Orciprenaline (n=4) .10μg/kg Terbutaline (n=4) 0.3μg/kg Trimetoquinol (n=4). 3μg/kg 60 Inhibition of Airway Resistance mean±S.E. 30 As you can see in this slide, Procaterol has a longer duration of bronchodilating action of more than 8 hours, which is much longer than those of salbutamol and terbutaline. 1 2 3 4 5 6 8 (hr.) Postｰadministration Kawamura et al: Unpublished Data (Internal Use)

Duration of Action of Meptin Tablets 60 70 80 90 100 110 120 130 140 150 160 (%) START Meptin 0.1mg Metaproterenol 20mg Salbutamol 4mg Trimetoquinol 6mg Control FEV1.0 Meptin tablet 50 µg This slide shows another evidence demonstrating the long duration of action of our product, Procaterol, Meptin lasting up to more than 12 hours, thus proving its beneficial effect especially when given at bedtime to patients suffering from nocturnal asthma. 18 20 22 0 2 4 6 8 10 12 PM AM Yakura, T. et. al.: Gendai Iryo. 10:1499 (1978)

Results of Clinical Study with Meptin Improvement of Sleep (%) 100 n = 94 (Acute Pediatric Bronchitis) Meptin 25mcg tablets 50 Clinical results have shown that our product, Procaterol, Meptin improved sleep in almost 50% of the patients in this study on the first day of administration, and in almost 100% of them on the 3rd day. This long duration of action of our product, Procaterol, Meptin not only provides restful sleep at night to asthmatic patients, but also benefits to their parents in case of pediatric patients and other relatives tasked with taking care of them as they don’t have to wake up in the wee hours of the morning just to attend to the need of the patient undergoing an attack. 53 1 53 2 53 3 53 4 52 5 50 6 48 7 44 (Days) (n) Matsuyama et. al.: Clinical Pediatrics, 43 (2), 373 (1990)

Dosage and Administration: Meptin® Syrup The usual adult dosage is 10 ml of Meptin® Syrup (50 µg of procaterol hydrochloride) once before bed or twice (in the morning and before bed) a day by oral route. The dosage in children 6 years of age or older is 5 ml of Meptin® Syrup (25 µg of procaterol hydrochloride) once before bed or twice (in the morning and before bed) a day by the oral route. The dosage in children less than 6 years of age is 0.25 ml of Meptin® Syrup (1.25 µg of procaterol hydrochloride) per Kg body weight once before bed or twice (in the morning and before bed) a day by the oral route. The dosage may be adjusted according to the patient’s age and severity of symptoms. Meptin® Syrup The usual adult dosage is 10 ml of Meptin® Syrup (50 µg of procaterol hydrochloride) once before bed or twice (in the morning and before bed) a day by oral route. The dosage in children 6 years of age or older is 5 ml of Meptin® Syrup (25 µg of procaterol hydrochloride) once before bed or twice (in the morning and before bed) a day by the oral route. The dosage in children less than 6 years of age is 0.25 ml of Meptin® Syrup (1.25 µg of procaterol hydrochloride) per Kg body weight once before bed or twice (in the morning and before bed) a day by the oral route. The dosage may be adjusted according to the patient’s age and severity of symptoms.

Dosage and Administration: Meptin® Tablet 50 µg The usual adult dosage of Meptin® Tablet is one tablet (50 µg), orally once before bed or twice (in the morning and before bed) per day. The dosage should be adjusted according to the patient’s age and severity of symptoms. Meptin® Tablet 25 µg The usual dose of Meptin® 25 µg tablet is two tablets (50 µg) once before bed or twice (in the morning and before bed) per day by the oral route. The dosage in children 6 years of age or older is one tablet (25 µg), once before bed or twice (in the morning and before bed) per day by the oral route. The dosage should be adjusted according to the patient’s age and severity of symptoms. This slide is just a reminder of the proper dosage and administration of Meptin Tablets. Meptin® Tablet 50 µg The usual adult dosage of Meptin® Tablet is one tablet (50 µg), orally once before bed or twice (in the morning and before bed) per day. The dosage should be adjusted according to the patient’s age and severity of symptoms. Meptin® Tablet 25 µg The usual dose of Meptin® 25 µg tablet is two tablets (50 µg) once before bed or twice (in the morning and before bed) per day by the oral route. The dosage in children 6 years of age or older is one tablet (25 µg), once before bed or twice (in the morning and before bed) per day by the oral route. The dosage should be adjusted according to the patient’s age and severity of symptoms.

MEPTIN: ORAL & INHALED DURATION OF ACTION ORAL: 10 to 12 hours ONSET OF ACTION ORAL: 30 to 60 minutes INHALED: 3 to 5 minutes Meptin is available in both oral and inhaled form. The difference is in the duration and onset of action for your patients.

Thank you for your time in listening to my presentation, doctor. As you can see, here is the line up of our respiratory products. Meptin Syrup, Tablets, and Swinghaler, together with Budesonide Obucort, are all approved for the relief of asthma symptoms. Meptin has been, and ever will be the reliable choice through the years for Asthma management and control.