Formoterol Generics
SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
Formoterol Generics 12 microgram powder for inhalation, hard capsule
QUALITATIVE AND QUANTITATIVE COMPOSITION
One hard capsule contains 12 micrograms formoterol fumarate dihydrate.
This is equivalent to a delivered dose (ex actuator) of 10 microgram of formoterol fumarate dihydrate.
Excipient: Formoterol Genericscontains lactose monohydrate, up to 25 mg per metered dose.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Inhalation powder, hard capsule
Hard and colourless capsule of approximately 16 mm long containing white coloured powder
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Formoterol Generics is indicated, as add on therapy to maintenance treatment with inhaled corticosteroids, for the relief of broncho-obstructive symptoms and prevention of exercise-induced symptoms in patients with asthma when adequate treatment with corticosteroids is not sufficient.
Formoterol Generics is also indicated for the relief of broncho-obstructive symptoms in patients with chronic obstructive pulmonary disease (COPD) .
4.2 Posology and method of administration
Use of doses above those normally required by the individual patient on more than 2 days per week is a sign of suboptimal disease control and maintenance treatment should be reassessed.
Formoterol Generics is not recommended for use in children below 6 years due to insufficient data on safety and efficacy.
Asthma
In asthma, Formoterol Generics can be used once or twice daily (‘regular dosage’), and as ‘relief medication’ to relieve acute broncho-obstructive symptoms.
Adults aged > 18 years:
Relief medication: 1 inhalation for the relief of acute broncho-obstructive symptoms.
Regular dosage: 1 inhalation once or twice daily. Some patients may need 2 inhalations once or twice daily.
Prevention of exercise-induced bronchoconstriction: 1 inhalation before exercise.
The daily dose for regular use should not exceed 4 inhalations, however occasionally up to a maximum of 6 inhalations (regular plus for relief)may be allowed within a 24-hour period. No more than 3 inhalations should be taken on any single occasion.
Children and adolescents, 6 years and older:
Relief medication: 1 inhalation for the relief of acute broncho-obstructive symptoms.
Regular dosage: 1 inhalation once or twice daily.
Prevention of exercise-induced bronchoconstriction: 1 inhalation before exercise.
The regular daily dose should not exceed 2 inhalations, however occasionally up to a maximum of 4 inhalations (regular plus for relief)may be allowed within a 24-hour period. No more than 1 inhalation should be taken on any single occasion.
COPD:
Regular dosage: 1 inhalation once or twice daily.
The daily dose for regular use should not exceed 2 inhalations.
If required, additional inhalations above those prescribed for regular therapy may be used for relief of symptoms, up to a maximum total daily dose of 4inhalations, (regular plus as required). More than 2 inhalations should not be taken on any single occasion.
Special patient groups: There are no special dosing requirements for elderly patients. There are no data available for use of Formoterol Generics in patients with hepatic or renal impairement (see also section 5.2).
Formoterol Generics is inspiratory flow driven which means that, when the patient inhales through the mouthpiece, the substance will follow the inspired air into the airways.
Note! It is important to instruct the patient to breathe in forcefully and deeply through the mouthpiece to ensure that an optimal dose is obtained.
It is important to instruct the patient never to chew or bite on the mouthpiece and never to use the inhaler if it has been damaged or if the mouthpiece has become detached.
The patient may not taste or feel any medication when using Formoterol Generics due to the small amount of drug dispensed.
Detailed instructions for use are packed together with each inhaler.
4.3 Contraindications
Known hypersensitivity to formoterol, or to lactose (which contains small amount of milk proteins).
4.4 Special warnings and precautions for use
Formoterol Generics should not be used (and is not sufficient) as the first treatment for asthma.
Asthmatic patients who require therapy with long-acting 2-agonists, should also receive optimal maintenance anti-inflammatory therapy with corticosteroids. Patients must be advised to continue taking their anti-inflammatory therapy after the introduction of Formoterol Generics even when symptoms decrease. Should symptoms persist, or treatment with 2-agonists need to be increased, this indicates a worsening of the underlying condition and warrants a reassessment of the maintenance therapy. AlthoughFormoterol Generics may be introduced as add-on therapy when inhaled corticosteroids do not provide adequate control of asthma symptoms, patients should not be initiated on Formoterol Generics during an acute severe asthma exacerbation, or if they have significantly worsening or acutely deteriorating asthma. Serious asthma-related adverse events and exacerbations may occur during treatment with Formoterol Generics. Patients should be asked to continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Formoterol Generics. Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Formoterol Generics. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Formoterol Generics should be used.
The maximum daily dose should not be exceeded. The long term safety of regular treatment at higher doses than 36 micrograms per day in adults with asthma, 18 micrograms per day in children with asthma and 18 micrograms per day in patients with COPD has not been established.
Frequent need of medication (i.e. prophylactic treatment e.g. corticosteroids and long-acting 2-agonists) for the prevention of exercise-induced bronchoconstriction several times every week, despite an adequate maintenance treatment, can be a sign of suboptimal asthma control, and warrants a reassessment of the asthma therapy and an evaluation of the compliance.
Caution should be observed when treating patients with thyrotoxicosis, phaeochromocytoma, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm or other severe cardiovascular disorders, such as ischaemic heart disease, tachyarrhythmias or severe heart failure.
Formoterol may induce prolongation of the QTc-interval. Caution should be observed when treating patients with prolongation of the QTc-interval and in patients treated with drugs affecting the QTc-interval (see 4.5).
Due to the hyperglycaemic effects of 2-agonists, additional blood glucose monitoring is recommended initially in diabetic patients.
Potentially serious hypokalaemia may result from 2-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatment with xanthine-derivatives, steroids and diuretics. The serum potassium levels should therefore be monitored.
As with other inhalation therapy, the potential for paradoxial bronchospasm should be considered. If it occurs, the treatment should be discontinued immediately and alternative therapy started (See section 4.8).
Formoterol Generics contains lactose monohydrate, up to 25 mg per metered dose. This amount does not normally cause problems in lactose intolerant people. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The excipient lactose contains small amounts of milk proteins. These may cause allergic reactions.
Children up to the age of 6 years should not be treated with Formoterol Generics, as no sufficient experience is available for this group.
4.5 Interaction with other medicinal products and other forms of interaction
No specific interaction studies have been carried out with <invented name>.
Concomitant treatment with other sympathomimetic substances such as other 2-agonists or ephedrinemay potentiate the undesirable effects of Formoterol Generics and may require titration of the dose.
Concomitant treatment with xanthine derivatives, steroids or diuretics such as thiazides and loop diuretics may potentiate a rare hypokalaemic adverse effect of 2-agonists. Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.
There is a theoretical risk that concomitant treatment with other drugs known to prolong the QTc-interval may give rise to a pharmacodynamic interaction with formoterol and increase the possible risk of ventricular arrhythmias. Examples of such drugs include certain antihistamines (e.g. terfenadine, astemizole, mizolastine), certain antiarrhythmics (e.g. quinidine, disopyramide, procainamide), erythromycin and tricyclic antidepressants.
There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.
The bronchodilating effects can be enhanced by anticholinergic drugs.
Beta-adrenergic blockers can weaken or inhibit the effect of Formoterol Generics. Formoterol Generics should therefore not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons.
4.6 Fertility, pregnancy and lactation
Fertility
There are no clinical data of the effect of Formoterol Generics on fertility. However, a somewhat reduced fertility in male rats was observed at high systemic exposure to formoterol (see section 5.3).
Pregnancy
There are no adequate data from the use of formoterol in pregnant women. In animal studies formoterol has caused implantation losses as well as decreased early postnatal survival and birth weight. The effects appeared at considerably higher systemic exposures than those reached during clinical use of Formoterol Generics .Treatment with Formoterol Generics may be considered at all stages of pregnancy if needed to obtain asthma control, and if the expected benefit to the mother is greater than any possible risk to the fetus. The potential risk for human is unknown (see section 5.3).
Breast-feeding
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 Formoterol Generics to women who are breastfeeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.
4.7 Effects on ability to drive and use machines
Formoterol Generics has no influence on the ability to drive and use machines..
4.8 Undesirable effects
The most commonly reported adverse events of 2-agonist therapy, such as tremor and palpitations, tend to be mild and disappear within days of treatment.
Adverse reactions, which have been associated with formoterol, are given below, listed by system organ class and frequency. Frequency are defined as: very common (1/10), common (1/100) and <1/10), uncommon (1/1 000 and < 1/100), rare (1/10 000 and < 1/1000) and very rare <1/10 000).
|
Cardiac disorders |
Common |
Palpitations |
|
Uncommon |
Tachycardia |
|
|
Rare |
Cardiac arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystoles. |
|
|
Very rare |
Angina pectoris, Prolongation of QTc interval |
|
|
Gastrointestinal disorders |
Rare |
Nausea |
|
Immune system disorders |
Rare |
Hypersensitivity reactions, e.g. bronchospasm, exanthema, urticaria, pruritus |
|
Metabolic and nutrition disorders |
Rare |
Hypokalemia |
|
Very rare |
Hyperglycemia |
|
|
Musculoskeletal, connective tissue and bone disorders |
Uncommon |
Muscle cramps |
|
Nervous system disorders |
Common |
Headache, tremor |
|
Very rare |
Taste disturbances, dizziness |
|
|
Psychiatric disorders |
Uncommon |
Agitation, restlessness, sleep disturbances |
|
Vascular disorders |
Very rare |
Variations in blood pressure |
As with all inhalation therapy, paradoxical bronchospasm may occur in very rare cases.( see section 4.4).
Treatment with 2-agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.
The excipient lactose contains small amounts of milk proteins. These may cause allergic reactions.
4.9 Overdose
There is limited clinical experience on the management of overdose. An overdose would likely lead to effects that are typical of 2-agonists: tremor, headache, palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycaemia, hypokalaemia, prolonged QTc-interval, arrythmia, nausea and vomiting. Supportive and symptomatic treatment is indicated.
Use of cardioselective beta-blockers may be considered, but only subject to extreme caution since the use of -adrenergic blocker medication may provoke bronchospasm. Serum potassium should be monitored.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Selective beta2-adrenergic agonist, ATC code: R03AC13.
Formoterol is a selective 2-adrenoceptor agonist that produces relaxation of bronchial smooth muscle. Formoterol thus has a bronchodilating effect in patients with reversible airways obstruction. The bronchodilating effect sets in rapidly, within 1-3 minutes after inhalation and has a mean duration of 12 hours after a single dose.
5.2 Pharmacokinetic properties
Absorption
Inhaled formoterol is rapidly absorbed. Peak plasma concentration is reached about 10 minutes after inhalation.
In studies the mean lung deposition of formoterol after inhalation via Turbuhaler ranged from 28-49% of the delivered dose (corresponding to 21-37% of the metered dose). The total systemic availability for the higher lung deposition was around 61% of the delivered dose (corresponding to 46% of the metered dose).
Distribution and metabolism:
Plasma protein binding is approximately 50%.
Formoterol is metabolised via direct glucuronidation and O-demethylation. The enzyme responsible for O-demethylation has not been identified. Total plasma clearance and volume of distribution has not been determined.
Elimination
The major part of the dose of formoterol is eliminated via metabolism. After inhalation 8-13% of the delivered dose (corresponding to 6-10% of the metered dose) of formoterol is excreted unmetabolised in the urine. About 20% of an intravenous dose is excreted unchanged in the urine. The terminal half-life after inhalation is estimated to be 17 hours.
Special populations:
The effect of decreased liver or kidney function on the pharmacokinetics of formoterol and the pharmacokinetics in the elderly is not known. As formoterol is primarily eliminated via liver metabolism an increased exposure can be expected in patients with severe liver cirrhosis.
5.3 Preclinical safety data
The effects of formoterol seen in toxicity studies in rats and dogs were mainly on the cardiovascular system and consisted of hyperaemia, tachycardia, arrhythmias and myocardial lesions. These effects are known pharmacological manifestations seen after the administration of high doses of 2-agonists.
A somewhat reduced fertility in male rats was observed at high systemic exposure to formoterol.
No genotoxic effects of formoterol have been observed in in-vitro or in vivo tests. In rats and mice a slight increase in the incidence of benign uterine leiomyomas has been observed. This effect is looked upon as a class-effect observed in rodents after long exposure to high doses of 2-agonists.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate which contains milk proteins
6.2 Incompatibilities
Not applicable
6.3 Shelf life
Alu/Alu blister: 2 years.
HDPE bottle: 3 years.
Shelf life after first opening of the bottle: 1 month.
6.4 Special precautions for storage
In Alu/Alu blisters: Store in the original package in order to protect from moisture
Do not store above 30 ºC.
In bottles: Store in the original package in order to protect from moisture.
This medicinal product does not require any special temperature storage conditions.
6.5 Nature and contents of container
1 inhaler + HDPE bottle with a Plastic cap with inviolable safety ring containing 60,
120 or 180 hard HPMC capsules.
1 inhaler + Alu/Alu Blister of 10, 30, 60, 120 or 180 hard HPMC capsules
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
To ensure proper administration of the drug, the patient should be shown how to use the inhaler by a physician or other health professional.
The capsules should be removed from the blister strip onlyimmediately before use
7. MARKETING AUTHORISATION HOLDER
To be completed nationally
8. MARKETING AUTHORISATION NUMBER(S)
To be completed nationally
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
2014-05-05
10. DATE OF REVISION OF THE TEXT
2016-02-01