Indications

This is indicated in conventional asthma treatment when a combination product (long-acting β2-agonist and inhaled corticosteroid) is appropriate: inhaled corticosteroid and long-acting 2-agonist.

Pharmacology

Salmeterol xinafoate is a selective, long-acting beta2 agonist used in the treatment of asthma and other diffuse forms of airway obstruction. Fluticasone propionate is a corticosteroid with predominantly glucocorticoid activity. Fluticasone propionate has been reported to have a local effect on the lungs with no systemic effect at usual doses.

Salmeterol protects against symptoms, and fluticasone propionate improves lung function and prevents exacerbations of the disease. This preparation may provide a more convenient treatment regimen for patients treated concomitantly with inhaled corticosteroids and agonists. The respective mechanisms of action of the two drugs are discussed below:

Salmeterol: Salmeterol is a long-acting (12 h) selective beta-adrenergic receptor agonist with a long side chain that binds to the outer part of the receiver.

Fluticasone propionate: Fluticasone propionate administered by inhalation at the recommended dose has potent anti-inflammatory glucocorticoid effects in the lungs, resulting in the reduction of symptoms and asthma attacks, with no adverse effects observed with systemic corticosteroids.

Dosage

Inhalation Aerosol:

• Adults and adolescents 12 years and older: 2 puffs of 25 µg Salmeterol and 50 µg Fluticasone Propionate twice daily or 2 puffs of 25 µg Salmeterol and 125 µg Fluticasone Propionate twice daily or 2 puffs of 25 µg Salmeterol and 250 µg Fluticasone Propionate twice daily.
• Children (4-12 years): 2 puffs of 25 µg salmeterol and 50 µg Fluticasone Propionate twice daily.

Inhalation Powder in Capsule (For Asthma):

• Adult and Adolescent (12 Years and Older): Salmeterol 50 µg & Fluticasone 100 µg or Salmeterol 50 µg & Fluticasone 250 µg twice daily (morning and evening, approximately 12 hours apart).
• The recommended starting dosages for Salmeterol 50 µg & Fluticasone 100 µg & Salmeterol 50 µg & Fluticasone 250 µg for patients aged 12 years and older are based upon the patient’s asthma severity.
• The maximum recommended dosage is Salmeterol 50 µg & Fluticasone 500 µg twice daily.
• Pediatric Patients (4 to 11 Years): For patients with asthma who are not controlled on an inhaled corticosteroid, the dosage is Salmeterol 50 µg & Fluticasone 100 µg twice daily (morning and evening, approximately 12 hours apart).

Inhalation Powder in Capsule (For COPD): Salmeterol 50 µg & Fluticasone 250 µg twice daily (morning and evening, approximately 12 hours apart). Rinsing the mouth after each inhalation is advised.

Inhalation Powder in Maxhaler (For Asthma): This is a molded plastic device containing a foil strip with 60 regularly placed blisters containing pre-dispensed inhalation powder. Patients should be made aware that Maxhaler must be used daily for optimum benefit, even when asymptomatic.

Adults and Adolescents (12 years and older)-

• 50/100 Maxhaler: One Inhalation twice daily
• 50/250 Maxhaler: One Inhalation twice daily
• 50/500 Maxhaler: One Inhalation twice daily

Children (4 years and older)-

• 50/100 Maxhaler: One Inhalation twice daily. The maximum licensed dose of fluticasone propionate delivered by this Maxhaler in children is 100 ug twice daily. There are no data available for use of this Maxhaler in children aged under 4 years.

Inhalation Powder in Maxhaler (For COPD):

• Maxhaler: One Inhalation twice daily
• Special patient groups: There is no need to adjust the dose in elderly patients or in those with renal impairment. There are no data available for use of this in patients with hepatic impairment.
• Using the Maxhaler: This is a patient-friendly, ready-to-use, and easy-to-grip device. Use as per instructions for use.

Administration

Using an Inhaler seems simple, but most patients do not know how to use it in the right way. If the Inhaler is used in the wrong way, less medicine can reach the lungs. Correct and regular use of the Inhaler will prevent or lessen the severity of asthma attacks.

Following simple steps can help to use Inhaler effectively (According to “National Asthma Guidelines for Medical Practitioners” published by Asthma Association):

• Take off the cap.
• Shake the inhaler (at least six times) vigorously before each use.
• If the inhaler is new or if it has not been used for a week or more, shake it well and release one puff into the air to make sure that it works.
• Breathe out as fully as comfortably possible & hold the inhaler upright.
• Place the actuator into the mouth between the teeth and close the lips around the mouthpiece.
• While breathing deeply and slowly through the mouth, press down firmly and add fully to the canister to release medicine.
• Remove the inhaler from the mouth. Continue holding your breath for at least 10 seconds or as long as it is comfortable.
• If the doctor has prescribed more than one inhalation per treatment, wait 1 minute between puffs (inhalations). Shake the inhaler well and repeat steps 4 to 7.
• After use, replace the cap on the mouthpiece. After each treatment, rinse your mouth with water.
• Check your technique in front of a mirror from time to time, if you see a white mist during the inhalation, you may not have closed your lips properly around the mouthpiece, or you may not be breathing in as you press the can. This indicates a failure of the technique. If this happens, repeat the procedure from step 4 carefully.

Instructions for Cleaning Inhaler: Clean your Inhaler at least once a week. Remove the canister and rinse the plastic actuator and cap in warm water but do not put the metal canister into water. Dry the actuator and cap thoroughly and gently replace the metal canister into the actuator with a twisting motion. Put the cap on the mouthpiece.

Interaction

Nonselective and selective beta-blockers should be avoided in patients with asthma unless there is a compelling reason for their use. Since very low plasma concentrations are achieved after inhalation, clinically significant drug interactions are unlikely. Caution is advised when co-administered with known strong inhibitors of CYP3A4 (eg, ketoconazole, ritonavir), due to the risk of increased systemic exposure to fluticasone propionate.

Contraindications

Patients who have a history of allergies to any ingredient are contraindicated.

Side Effects

Since this preparation contains salmeterol and fluticasone propionate, the type and severity of side effects associated with each compound can be expected. There was no incidence of additional adverse events following the concomitant use of the two compounds. Adverse events associated with salmeterol or fluticasone propionate are listed below.

Salmeterol: Pharmacologic adverse reactions with beta2 antagonisms, such as tremors, subjective palpitations, and headache, have been reported, but tend to be transient and subside with usual treatment. Cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia, and extrasystoles) can occur, usually in susceptible patients. Arthralgia and hypersensitivity reactions have been reported, including rash, edema, and angioedema. Oropharyngeal irritation has been reported. Rare cases of muscle cramps have been reported.

Fluticasone propionate: Hoarseness and candida (thrush) infections of the mouth and throat may occur in some patients. Skin hypersensitivity reactions have been reported. Rare cases of facial and oropharyngeal edema have been reported. Hoarseness and the incidence of candidiasis can be reduced by rinsing the mouth with water after using the salmeterol/fluticasone propionate inhaler.

Pregnancy & Lactation

Use during pregnancy and lactation should only be considered if the expected benefit to the mother outweighs any possible risk to the fetus or child. There is insufficient experience with the use of salmeterol xinafoate and fluticasone propionate during pregnancy and lactation. No data are available for breast milk.

Precautions & Warnings

Additional corticosteroid therapy should be considered, including the use of antibiotics if the infection is present. As with all inhaled corticosteroids, this preparation should be used with caution in patients with active or recovered pulmonary tuberculosis. This preparation should be used with caution in patients with thyrotoxicosis.

Therapeutic Class

Long-acting selective β-adrenoceptor stimulants, Respiratory corticosteroids

Storage Conditions

Do not puncture, rupture, or incinerate pressurized containers, even if they are obviously empty. Avoid storing in direct sunlight or high temperature. Store below 30°C. Keep out of eyes. Keep away from children.

Generic

Salmeterol + Fluticasone Propionate

Pharmaceutical Name

Healthcare Pharmaceuticals Ltd.