Formocort Metered-Dose Inhaler (MDI)

This inhalation capsule is used for dry powder inhaler. It is intended for oral inhalation only. It is a combination of Formoterol Fumarate Dihydrate BP and Budesonide BP. Budesonide is a glucocorticosteroid which when inhaled has a dose-dependent anti-inflammatory action in the airways, resulting in reduced symptoms and fewer asthma exacerbations. Inhaled Budesonide has less severe adverse effects than systemic corticosteroids.The exact mechanism responsible for the anti-inflammatory effect of glucocorticosteroids is unknown. Formoterol is a selective β2 adrenoceptor agonist that when inhaled results in rapid and long-acting relaxation of bronchial smooth muscle in patients with reversible airways obstruction. The bronchodilating effect is dose-dependent, with an onset of effect within 1-3 minutes. The duration of effect is at least 12 hours after a single dose.

Budesonide: It is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma.

Formoterol Fumarate Dihydrate: It is a long-acting, selective β2 - adrenergic agonist with a rapid onset of action. Inhaled Formoterol Fumarate Dihydrate BP acts locally in the lungs as a bronchodilator. The pharmacological effects of β2-adrenoceptor agonist drugs are attributable to the stimulation of intracellular adenyl cyclase, the enzyme that catalyses the conversion of adenosine triphosphate (ATP) to cyclic AMP. Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibit the release of mediators of immediate hypersensitivity from the cells, especially from mast cells.

Inhaler (For Asthma)-

• Adults and adolescents (12 years and older): The recommended maintenance dose is 1 puff twice daily or 2 puffs once daily. For some patients a maintenance dose of 2 puffs twice daily may be appropriate (for 160/4.5 mcg/inhalation only). Patients should take 1 additional puff as needed in response to symptoms. If symptoms persist after a few minutes, the additional puff should be taken. Not more than 6 puffs should be taken on any single occasion.

• Children: The usual maintenance dose is 1 -2 puffs once or twice daily. Patients should take 1 additional puff as needed in response to symptoms. If symptoms persist after a few minutes, the additional puff should be taken. Not more than 4 puffs should be taken on any single occasion.

Inhalation Capsule (For Asthma): There are two alternative dosage regimens for the treatment of asthma with Budesonide and Formoterol combination. Budesonide and Formoterol 100 & 200 Inhalation Capsule maintenance and reliever therapy.
Adults and adolescents (12 years and older):

• Maintenance dose: Budesonide and Formoterol 100 & 200 Inhalation Capsule twice daily
• Reliever dose: 1 additional Inhalation Capsule as needed in response to symptoms. If symptoms persist after a few minutes, an additional Inhalation Capsule should be taken. Not more than 6 Inhalation Capsule should be taken on any single occasion. A total daily dose of more than 8 Inhalation Capsule is not normally needed, however, a total daily dose of up to 12 Inhalation Capsule can be used temporarily.

Children (4 years and older):

• Maintenance dose: Budesonide and Formoterol 100 Inhalation Capsule once daily.
• Reliever dose: 1 additional Inhalation Capsule as needed in response to symptoms. If symptoms persist after a few minutes, an additional Inhalation Capsule should be taken. Not more than 4 Inhalation Capsule should be taken on any single occasion. A total daily dose of more than 4 Inhalation Capsule is not normally needed, however, a total daily dose of up to 8 Inhalation Capsule could be used temporarily.

Inhalation Capsule (For COPD): Adults (40 years and older)

• 200 Inhalation Capsule: 2 Inhalation Capsule twice daily. Maximum daily maintenance dose: 4 Inhalation Capsule
• 400 Inhalation Capsule: 1 Inhalation Capsule twice daily. Maximum daily maintenance dose: 2 Inhalation Capsule.

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):

1. Take off the cap.
2. Shake the inhaler (at least six times) vigorously before each use.
3. 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.
4. Breathe out as full as comfortably possible & hold the inhaler upright.
5. Place the actuator into mouth between the teeth and close lips around the mouthpiece.
6. While breathing deeply and slowly through the mouth, press down firmly add fully on the canister to release medicine.
7. Remove the inhaler from mouth. Continue holding breath for at least for 10 seconds or as long as it is comfortable.
8. If 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.
9. After use, replace the cap on the mouthpiece. After each treatment, rinse mouth with water.
10. 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 mouthpiece, or you may not be breathing in as you press the can. This indicates failure of technique. If this happens, repeat the procedure from step 4 carefully.

Instructions for Cleaning Inhaler: Clean your Inhaler at least once a week. Remove 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.

Co-administration with strong cytochrome P450 3A4 inhibitors (e.g., ritonavir) should be avoided as they may cause increased systemic corticosteroid effects. Co-administration with Monoamine oxidase inhibitors and tricyclic antidepressants should be with extreme caution as they may potentiate effect of formoterol on vascular system. Beta-blockers should be use with caution as they may block bronchodilatory effects of beta-agonists and produce severe bronchospasm. Co-administration of Formocort with diuretics should be with caution, as they may cause electrocardiographic changes and/or hypokalemia associated with nonpotassium- sparing diuretics may worsen with concomitant beta-agonists.

This is contraindicated in the following conditions-

• Primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required.
• Hypersensitivity to any of the ingredients in this preparation.

As the combination inhaler contains Formoterol Fumarate and Budesonide, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no incidence of additional adverse events following concurrent administration of the two compounds. Adverse events, which have been associated with Formoterol Fumarate Dihydrate and Budesonide, are given below:

Formoterol Fumarate: Tremor, palpitations and headache are common adverse events. Cardiac arrhythmias, muscle cramps and hypersensitivity reactions, including rash, oedema and angiooedema are uncommon and rare.

Budesonide: Hoarseness, candida infection in the oropharynx and throat irritation may occur in some patients. Cutaneous hypersensitivity reactions, respiratory tract infections, immunosuppression, growth effect in children, glaucoma & cataract have been reported.

For this combination or the concomitant treatment with Formoterol and Budesonide, no clinical data on exposed pregnancies are available. Data from an embryo-foetal development study in the rat, showed no evidence of any additional effect from the combination.There are no adequate data from use of Formoterol in pregnant women. In animal studies Formoterol has caused adverse effects in reproduction studies at very high systemic exposure levels. Budesonide is excreted in breast milk. However, at therapeutic doses no effects on the suckling child are anticipated. It is not known whether Formoterol passes into human breast milk. In rats, small amounts of Formoterol have been detected in maternal milk. Administration of this combination to women who are breast-feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

Caution should be taken in patients with diabetes mellitus, thyrotoxicosis, untreated hypokalaemia, severe hypertension and severe cardiovascular disorders, such as ischaemic heart disease, tachycardia or severe heart failure, glaucoma and cataract, hypercorticism. Paradoxical bronchospasm may occur, with an immediate increase in wheezing and shortness of breath after dosing. If the patient experiences paradoxical bronchospasm the medication should be discontinued immediately.

It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be re evaluated with the aim of reducing the dose of inhaled corticosteroid. The benefits of the corticosteroid therapy and the possible risks of growth suppression must be carefully weighed. In addition consideration should be given to referring the patient to a paediatric respiratory specialist.

An overdose of Formoterol would likely lead to effects that are typical for (32 adrenoceptor agonists: tremor, headache, palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycaemia, hypokalaemia, prolonged QTc-interval, arrhythmia, nausea and vomiting. Supportive and symptomatic treatment may be indicated. A dose of 90 micrograms administered during three hours in patients with acute bronchial obstruction raised no safety concerns. Acute overdosage with Budesonide, even in excessive doses, is not expected to be a clinical problem. When used chronically in excessive doses, systemic glucocorticosteroid effects, such as hypercorticism and adrenal suppression, may appear.

Inhalation capsules must not be swallowed. Only to be used with inhalation device. Keep away from light and wet place. Store at or below 25°C temperature. Keep out of reach of children. Remove Inhalation capsule from the blister pack only immediately before use it in the inhalation device as Inhalation capsule exposed to moisture may not be pierced easily.