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FORMATRIS NOVOLIZER 12 MICROGRAMS PER ACTUATION INHALATION POWDER

Active substance(s): FORMOTEROL FUMARATE DIHYDRATE MICRONISED / FORMOTEROL FUMARATE DIHYDRATE MICRONISED / FORMOTEROL FUMARATE DIHYDRATE MICRONISED

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Formatris Novolizer® 12 micrograms per actuation inhalation powder

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each metered dose contains 12 micrograms formoterol fumarate dihydrate
(corresponding to one delivered dose leaving the mouthpiece of 10.2 micrograms
formoterol fumarate dihydrate equivalent to 8.36 micrograms formoterol).
For a full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM
Inhalation powder
White powder

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Formatris Novolizer 12 micrograms is indicated in adults, adolescents and children
aged 6 to 12 years.
Formatris Novolizer 12 micrograms is indicated for the long-term symptomatic
treatment of persistent, moderate to severe asthma in patients requiring regular longacting β2 agonist therapy in combination with inhaled anti-inflammatory therapy (with
or without oral glucocorticoids).
Glucocorticoid therapy should be continued on a regular basis.
Formatris Novolizer 12 micrograms is also indicated for the relief of bronchoobstructive symptoms in patients with chronic obstructive pulmonary disease (COPD)
requiring long-acting bronchodilatory therapy.

4.2

Posology and method of administration
For inhalation use

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.
Asthma:
Adults (including older people) and adolescents over 12 years of age:
Regular Maintenance Therapy:
1 inhalation (12 micrograms) to be inhaled twice daily. For more severe disease this
dose regimen can be increased to 2 inhalations (24 micrograms) to be inhaled twice
daily.
The maximum daily dose is 4 inhalations (2 inhalations inhaled twice daily)
corresponding to 48 micrograms.

Paediatric population
Children 6 years and older:
Regular Maintenance Therapy:
1 inhalation (12 micrograms) to be inhaled twice daily. For more severe disease this
dose regimen can be increased to 2 inhalations (24 micrograms) to be inhaled twice
daily but only after assessment by a physician.
The regular daily dose should not exceed 2 inhalations (24 micrograms), however,
occasionally up to a maximum of 4 inhalations (corresponding to 48 micrograms)
may be allowed within a 24-hours period.
Children below 6 years of age
Formatris Novolizer is not recommended for use in children under the age of 6 years
as insufficient experience is available in this age group.
COPD:
Adults (including older people) and adolescents over 12 years of age:
Regular dosage: 1 inhalation (12 micrograms) twice daily.
The daily dose for regular use should not exceed 2 inhalations (24 micrograms).
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 4 inhalations
corresponding to 48 micrograms (regular plus as required). More than 2 inhalations
should not be taken on any single occasion.
The use of formoterol is indicated for those patients receiving inhaled corticosteroids
where further regular symptomatic treatment of asthma is required in addition to
inhaled corticosteroids.
Although formoterol has a rapid onset of action, long-acting inhaled bronchodilators
(as formoterol) should be used for maintenance bronchodilator therapy only.
Formoterol is not intended to relieve acute asthma attacks. In the event of an acute
attack, a short acting β2 agonist should be used.
Patients should be advised not to stop or change their steroid therapy when Formatris
Novolizer is introduced.
Older people and patient with renal or hepatic impairment
No adjustment of dose should be required in the elderly, or in patients with renal or
hepatic impairment at the recommended normal doses. (See section 4.4.)

Mode of treatment:
In order to ensure that the active substance optimally reaches the intended site of
action it is necessary to inhale steadily, deeply and as rapidly as possible (to the
maximum inhalation). A clearly audible click and a colour change in the control
window indicate that inhalation has been performed correctly. If an audible click is
not heard and there is no colour change in the control window, inhalation should be
repeated. The inhaler remains locked until inhalation is performed correctly.
Usage and handling of the Novolizer

Lid

Refilling
1. Lightly press together the ribbed surfaces on both sides of the lid, move the lid
forwards and lift off.
2. Remove the protective aluminium foil from the cartridge box and take out the
new cartridge.
3. Insert the cartridge into the Novolizer with the dosage counter facing the
mouthpiece.
4. Replace the lid into the side guides from above and push down flat towards the
dosage button until it snaps into place. The cartridge can be left in the Novolizer
until it has been used up, or for up to 6 months after insertion.
Note: Formatris Novolizer 12 micrograms cartridges may only be used in the
Novolizer powder inhaler.
Usage
1. Whenever possible, sit or stand while inhaling. When using the Novolizer always
keep it horizontal. First remove the protective cap.
2. Completely depress the coloured dosage button. A loud double click will be heard
and the colour of the control window (lower) will change from red to green. Then
release the coloured dosage button. The colour green in the window indicates that
the Novolizer is ready for use.
3. Exhale as far as possible (but not into the powder inhaler).

4. Put the lips around the mouthpiece. Inhale the powder with a deep breath. During
this breath a loud click should be heard, indicating correct inhalation. Hold the
breath for a few seconds and then continue with normal breathing.
Note: If the patient needs to take more than 1 actuation at a time, steps 2 - 4 should be
repeated
5. Replace the protective cap on the mouthpiece - the inhalation procedure is now
complete.
6. The number in the top window indicates the number of inhalations left.
Note: The coloured dosage button should only be pressed immediately before
inhalation.
A double inhalation in error is not possible with the Novolizer. The click sound and
the change of colour in the control window indicate that inhalation has been
performed correctly. If the colour of the control window does not change, then
inhalation should be repeated. If inhalation is not completed correctly after several
attempts, then the patient should consult the doctor/physician.
Cleaning
The Novolizer should be cleaned at regular intervals, but at least every time the
cartridge is changed. Instructions on how to clean the device can be found in the
brochure operating instructions in the carton.
Note: In order to ensure correct use of the inhaler, patients should receive thorough
instructions on how to use the device. Children should only use this product under the
supervision of an adult.

4.3

Contraindications
Hypersensitivity to the active substance formoterol or to the excipient lactose.

4.4

Special warnings and precautions for use
Formatris Novolizer 12 micrograms should not be used (and is not sufficient) as the
first treatment for asthma.
Asthmatic patients who require therapy with long-acting β2 agonists, should also
receive optimal maintenance anti-inflammatory therapy with corticosteroids. Patients
must be advised to continue taking their anti-inflammatory therapy and must be told
that the dose of anti-inflammatory therapy should not be decreased following the
introduction of formoterol without medical advice even when symptoms improve.
Should symptoms persist or worsen or the number of doses of β2 agonists required to
control symptoms increases, this usually indicates a worsening of the underlying
condition and the patients should be told to contact their doctor in order that their
asthma and its treatment can be reassessed.
Although Formatris Novolizer 12 micrograms may be introduced as add-on therapy
when inhaled corticosteroids do not provide adequate control of asthma symptoms,
patients should not be initiated on Formatris Novolizer 12 micrograms 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 Formatris Novolizer 12 micrograms. Patients should be asked to continue
treatment but to seek medical advice if asthma symptoms remain uncontrolled or
worsen after initiation on Formatris Novolizer 12 micrograms.
Once asthma symptoms are controlled, consideration may be given to gradually
reducing the dose of Formatris Novolizer 12 micrograms. Regular review of patients
as treatment is stepped down is important. The lowest effective dose of Formatris
Novolizer 12 micrograms should be used.
Formoterol should only be used in patients requiring treatment with long-acting
bronchodilators (see section 4.1) and should not be used as an alternative to shortacting β2 agonists in the event of an acute attack. In the event of an acute attack, a
short-acting β2 agonist must be used.
The maximum daily dose should not be exceeded. The long-term safety of regular
treatment at higher doses than 4 inhalations per day in adults with asthma, 2
inhalations per day in children with asthma and 2 inhalations per day in patients with
COPD, has not been established.
Frequent need of medication for the prevention of exercise-induced
bronchoconstriction (EIB) can be a sign of suboptimal asthma control, and warrants a
reassessment of the asthma therapy and an evaluation of compliance. If the patient
needs prophylactic treatment for EIB several times every week despite adequate
maintenance treatment (e.g. corticosteroids and long-acting β2 agonists), the total
asthma management should be reassessed by a specialist.
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, cardiac arrhythmias,
especially third degree atrioventricular block , or severe heart failure. An adjustment
of the dose of formoterol may be considered.
Formoterol may induce prolongation of the QTc-interval. Caution should be observed
when treating patients with prolongation of the QTc-interval (see section 4.5).
Due to the hyperglycaemic effects of β2 agonists, additional blood glucose monitoring
is recommended initially in diabetic patients.
Potentially serious hypokalaemia may result from β2 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. Special caution is advised if theophylline and
formoterol are used concomitantly in patients with pre-existing cardiac disease.
As with other inhalation therapy there is a risk of paradoxical bronchospasm. If this
occurs the patient will experience an immediate increase in wheezing and shortness of
breath after dosing which should be treated straightaway with a fast-acting inhaled
bronchodilator. Formatris Novolizer should be discontinued immediately, the patient
should be assessed and, if necessary, alternative therapy instituted.
Formatris Novolizer 12 micrograms contains 11.488 mg lactose per single dose. This
amount does not normally cause problems in lactose intolerant people.
Lactose may contain small amounts of milk protein.
Children up to the age of 6 years should not be treated with formoterol, as insufficient
experience is available for this age group.

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 metabolism, increased exposure can be expected in patients
with severe liver cirrhosis.

4.5

Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed with Formatris Novolizer.
Concomitant treatment with other sympathomimetic substances such as other β2
agonists or ephedrine may potentiate the undesirable effects of formoterol and may
require titration of the dose.
Concomitant treatment with xanthine derivatives, steroids or diuretics such as
thiazides and loop diuretics may potentiate a possible hypokalaemic adverse effect of
β2 agonists. Hypokalaemia may increase the susceptibility to arrhythmias in patients
who are treated with digitalis glycosides.
The concomitant use with oral corticosteroids might increase hyperglycaemic effects.
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), phenothiazines,
erythromycin and tricyclic antidepressants.
Administration of formoterol to patients being treated with monoamine oxidase
inhibitors (or having been treated during the past 14 days) or tricyclic antidepressants
should be performed with caution, since the action of β2 adrenergic stimulants on the
cardiovascular system may be potentiated.
In addition L-Dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance
towards β2 sympathomimetics.
There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia
with halogenated hydrocarbons.
Beta-adrenergic blockers can weaken or inhibit the effect of formoterol. Formoterol
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 only limited data with regard to fertility (see section 5.3). Reproduction
studies in rats revealed no impairment of fertility at oral doses up to 3 mg/kg
(approximately 1000 times the recommended daily inhalation dose of 24 µg in human
on a mg/m2 basis).
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. Treatment with
Formoterol 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.
Lactation
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 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 has no or negligible influence on the ability to drive or use machines.

4.8

Undesirable effects
The most commonly reported adverse events of β2 agonist therapy, such as tremor
and palpitations, tend to be mild and disappear within a few days of treatment.
Adverse reactions, which have been associated with formoterol are given below listed
by system organ class and frequency. Frequencies are defined as:
Very common (> 1/10); Common (> 1/100 to < 1/10); Uncommon (> 1/1,000 to <
1/100);
Rare (> 1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (cannot be
estimated from the available data)
Organ System

Frequency

Immune system disorders

Rare

Metabolism and nutrition
disorders

Rare
Very rare

Adverse drug reaction
Hypersensitivity reactions, e.g.
bronchospasm, exanthema, urticaria,
pruritus, angiooedema
Hypokalaemia/ Hyperkalaemia
Hyperglycaemia

Psychiatric disorders

Uncommon

Agitation, restlessness, sleep disturbance

Common

Headache, tremor

Rare

Nervousness

Very rare

Taste disturbance, dizziness

Common
Uncommon

Palpitations
Tachycardia
Cardiac arrhythmias, e.g. atrial
fibrillation, supraventricular tachycardia,
extrasystoles

Nervous system disorders

Cardiac disorders

Rare

Very rare

Angina pectoris, prolongation of QTcinterval

Organ System
Vascular disorders
Respiratory, thoracic and
mediastinal disorders
Gastrointestinal disorders
Musculoskeletal and
connective tissue disorders

Frequency
Very rare

Adverse drug reaction
Variations in blood pressure

Uncommon

oropharyngeal irritation

Rare

Nausea

Uncommon

Muscle cramps

As with all inhalation therapy, paradoxical bronchospasm may occur in rare cases.
Treatment with β2 agonists may result in an increase in blood levels of insulin, free
fatty acids, glycerol and ketone bodies.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9

Overdose
There is limited clinical experience in the management of overdose. An overdose
would likely lead to effects that are typical of β2 agonists: tremor, headache,
palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycaemia,
hypokalaemia, prolonged QTc -interval, arrhythmia, 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 β adrenergic blocker medication may provoke bronchospasm.
Serum potassium levels should be monitored.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: selective β2 agonist, formoterol
ATC code: R03AC13
Formoterol is a selective β2 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.

Clinical studies indicated that the lung deposition of formoterol after inhalation via
the Novolizer is within the range of other inhaler products containing formoterol.
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 have not been determined.
Elimination
The major part of the dose of formoterol is eliminated via metabolism. After
inhalation with a similar powder inhaler device 8-13% of the delivered dose of
formoterol was 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 8 hours.

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 β2 agonists.
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. 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 β2 agonists.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose monohydrate.

6.2

Incompatibilities
Not applicable

6.3

Shelf life


Formatris Novolizer 12 micrograms
Shelf life of the medicinal product as packaged for sale: 3 years
Shelf life after first opening the cartridge container: 6 months



Novolizer device
Shelf life before first use: 4 years
In-use shelf life: 1 year

Note: The functioning of the Novolizer has been demonstrated in tests for 2000
metered doses. This amount of metered doses is not expected to be exceeded during
one year of normal dosage.

6.4

Special precautions for storage
Store in the original package.
After first opening the cartridge cylinder: Store below 25 °C. Store protected from
moisture.

6.5

Nature and contents of container
The inhaler (mouth- piece) is made of polyethylene and the cartridge is made of
polystyrole.
Pack sizes:
1 powder inhaler and 1 cartridge (polystyrene / polypropylene) with at least 60
actuations.
1 powder inhaler and 2 cartridges (polystyrene / polypropylene) with at least 60
actuations each.
Refill packs:
1 cartridge (polystyrene / polypropylene) with at least 60 actuations
2 cartridges (polystyrene / polypropylene) with at least 60 actuations each
3 cartridges (polystyrene / polypropylene) with at least 60 actuations each
Hospital packs:
Pack with 10 x (1 powder inhaler and 1 cartridge (polystyrene / polypropylene) with
at least 60 actuations)
“Not all pack sizes may be marketed”

6.6

Special precautions for disposal
No special requirement.

7

MARKETING AUTHORISATION HOLDER
MEDA Pharmaceuticals Ltd
Skyway House
Parsonage Road
Takeley
Bishop’s Stortford
CM22 6PU
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 15142/0081

9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
20/11/2012

10

DATE OF REVISION OF THE TEXT
22/05/2014

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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