Formatide Inhalation Capsule 400mcg+12mcg

Product Information

FORMATIDE HFA

Formatide® HFA

Formoterol Fumarate Dihydrate & Budesonide

Presentation

Formatide 4.5/80 HFA: Each metered dose actuation delivers FormoterolFumarateDihydrate BP 4.5mcg and Budesonide BP 80mcg.

Formatide 4.5/160 HFA: Each metered dose actuation delivers FormoterolFumarateDihydrate BP 4.5mcg and Budesonide BP 160mcg.

Indications

Asthma: Formatide is indicated in the regular treatment of asthma where use of a combination (inhaled corticosteroid and

long-acting beta 2 adrenoceptor agonist) is appropriate:

– patients not adequately controlled with inhaled corticosteroids and “as needed” inhaled short-acting beta 2 adrenoceptor

agonists or

– patients already adequately controlled on both inhaled corticosteroids and long-acting beta 2 adrenoceptor agonists.

COPD: Symptomatic treatment of patients with severe COPD (FEV1 < 50% predicted normal) and a history of repeated exacerbations,

who have significant symptoms despite regular therapy with long-acting bronchodilators.

Dosage and Administration

Route of administration: For inhalation use.

Asthma: Formatide is not intended for the initial management of asthma. The dosage of the components of Formatide is individual

and should be adjusted to the severity of the disease. This should be considered not only when treatment with combination products

is initiated but also when the maintenance dose is adjusted. If an individual patient should require a combination of doses other

than those available in the combination inhaler, appropriate doses of beta 2 adrenoceptor agonists and/or corticosteroids by

individual inhalers should be prescribed.

The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. Patients should be regularly

reassessed by their prescriber / health care provider so that the dosage of Formatide remains optimal. When long-term control of

symptoms is maintained with the lowest recommended dosage, then the next step could include a test of inhaled corticosteroid

alone.

For Formatide there are two treatment approaches:

1. Formatide maintenance therapy: Formatide is taken as regular maintenance treatment with a separate rapid-acting bronchodilator

as rescue.

2. Formatide maintenance and reliever therapy: Formatide is taken as regular maintenance treatment and as needed in response to

symptoms.

Formatide maintenance therapy

Patients should be advised to have their separate rapid-acting bronchodilator available for rescue use at all times.

Recommended doses: Adults (18 years and older): 1-2 inhalation twice daily. Some patients may require up to a maximum of 4

inhalations twice daily.

Adolescents (12 – 17 years): 1-2 inhalations twice daily.

In usual practice when control of symptoms is achieved with the twice daily regimen, titration to the lowest effective dose could

include Formatide given once daily, when in the opinion of the prescriber, a long-acting bronchodilator would be required to

maintain control.

Increasing use of a separate rapid-acting bronchodilator indicates a worsening of the underlying condition and warrants a

reassessment of the asthma therapy.

Children (6 years and older): A lower strength is available for children 6-11 years.

Children under 6 years: As only limited data are available, Formatide is not recommended for children younger than 6 years.

Formatide maintenance and reliever therapy:

Patients take a daily maintenance dose of Formatide and in addition take Formatide as needed in response to symptoms. Patients

should be advised to always have Formatide available for rescue use.

Formatide maintenance and reliever therapy should especially be considered for patients with:

* inadequate asthma control and in frequent need of reliever medication

* asthma exacerbations in the past requiring medical intervention

Close monitoring for dose-related adverse effects is needed in patients who frequently take high numbers of Formatide as-needed

inhalations.

Recommended doses: Adults (18 years and older): The recommended maintenance dose is 2 inhalations per day, given either as one

inhalation in the morning and evening or as 2 inhalations in either the morning or evening. For some patients a maintenance dose

of 2 inhalations twice daily may be appropriate. Patients should take 1 additional inhalation as needed in response to symptoms.

If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be taken on

any single occasion.

A total daily dose of more than 8 inhalations is not normally needed; however, a total daily dose of up to 12 inhalations could be

used for a limited period. Patients using more than 8 inhalations daily should be strongly recommended to seek medical advice.

They should be reassessed and their maintenance therapy should be reconsidered.

Children and adolescents under 18 years: Formatide maintenance and reliever therapy is not recommended for children and

adolescents.

COPD:

Recommended doses: Adults: 2 inhalations twice daily

Special patient groups: There are no special dosing requirements for elderly patients. There are no data available for use of

Formatidei in patients with hepatic or renal impairment. As budesonide and formoterol are primarily eliminated via hepatic

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

Contra-indications, warnings, etc.

Contra-indications: Hypersensitivity (allergy) to budesonide, formoterol or lactose (which contains small amounts of milk

proteins).

Precautions: It is recommended that the dose is tapered when the treatment is discontinued and should not be stopped abruptly.

If patients find the treatment ineffective, or exceed the highest recommended dose of Formatide, medical attention must be sought.

Sudden and progressive deterioration in control of asthma or COPD is potentially life threatening and the patient should undergo

urgent medical assessment. In this situation, consideration should be given to the need for increased therapy with corticosteroids

e.g. a course of oral corticosteroids, or antibiotic treatment if an infection is present.

Patients should be advised to have their rescue inhaler available at all times, either Formatide (for asthma patients using

Formatide as maintenance and reliever therapy) or a separate rapid-acting bronchodilator (for all patients using Formatide as

maintenance therapy only). Patients should be reminded to take their Formatide maintenance dose as prescribed, even when

asymptomatic. The prophylactic use of Formatide, e.g. before exercise, has not been studied. The reliever inhalations of Formatide

should be taken in response to symptoms but are not intended for regular prophylactic use, e.g. before exercise. For such use, a

separate rapid-acting bronchodilator should be considered.

Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Formatide. Regular review of

patients as treatment is stepped down is important. The lowest effective dose of Formatide should be used.

Patients should not be initiated on Formatide during an exacerbation, or if they have significantly worsening or acutely

deteriorating asthma. Serious asthma-related adverse events and exacerbations may occur during treatment with Formatide. Patients

should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation

with Formatide.

As with other inhalation therapy, paradoxical bronchospasm may occur, with an immediate increase in wheezing and shortness of

breath, after dosing. If the patient experiences paradoxical bronchospasm Formatide should be discontinued immediately, the

patient should be assessed and an alternative therapy instituted, if necessary. Paradoxical bronchospasm responds to a

rapid-acting inhaled bronchodilator and should be treated straightaway.

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects

are much less likely to occur with inhalation treatment than with oral corticosteroids. Possible systemic effects include

Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone

mineral density, cataract and glaucoma, and more rarely, a range of psychological or behavioural effects including psychomotor

hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

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 to the lowest dose

at which effective control of asthma is maintained, if possible. 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. Limited data from long-term studies suggest that most children and adolescents treated with

inhaled budesonide will ultimately achieve their adult target height. However, an initial small but transient reduction in growth

(approximately 1 cm) has been observed. This generally occurs within the first year of treatment.

Potential effects on bone density should be considered particularly in patients on high doses for prolonged periods that have

co-existing risk factors for osteoporosis. Long-term studies with inhaled budesonide in children at mean daily doses of 400

micrograms (metered dose) or in adults at daily doses of 800 micrograms (metered dose) have not shown any significant effects on

bone mineral density. No information regarding the effect of Formatide at higher doses is available. If there is any reason to

suppose that adrenal function is impaired from previous systemic steroid therapy, care should be taken when transferring patients

to Formatide therapy.

The benefits of inhaled budesonide therapy would normally minimise the need for oral steroids, but patients transferring from oral

steroids may remain at risk of impaired adrenal reserve for a considerable time. Recovery may take a considerable amount of time

after cessation of oral steroid therapy and hence oral steroid-dependent patients transferred to inhaled budesonide may remain at

risk from impaired adrenal function for some considerable time. In such circumstances HPA axis function should be monitored

regularly.

The prolonged treatment with high doses of inhaled corticosteroids, particularly higher than recommended doses, may also result in

clinically significant adrenal suppression. Therefore additional systemic corticosteroid cover should be considered during periods

of stress such as severe infections or elective surgery. Rapid reduction in the dose of steroids can induce acute adrenal crisis.

Symptoms and signs which might be seen in acute adrenal crisis may be somewhat vague but may include anorexia, abdominal pain,

weight loss, tiredness, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension and hypoglycaemia.

Treatment with supplementary systemic steroids or inhaled budesonide should not be stopped abruptly.During transfer from oral

therapy to Formatide, a generally lower systemic steroid action will be experienced which may result in the appearance of allergic

or arthritic symptoms such as rhinitis, eczema and muscle and joint pain. Specific treatment should be initiated for these

conditions. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases, symptoms such as tiredness,

headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of oral glucocorticosteroids is

sometimes necessary.

To minimise the risk of oropharyngeal candida infection, thepatient should be instructed to rinse their mouth out with water after

inhaling the maintenance dose. If oropharyngeal thrush occurs, patients should also rinse their mouth with water after the

as-needed inhalations. Concomitant treatment with itraconazole, ritonavir or other potent CYP3A4 inhibitors should be avoided. If

this is not possible the time interval between administration of the interacting drugs should be as long as possible. In patients

using potent CYP3A4 inhibitors, Formatide maintenance and reliever therapy is not recommended.

Formatide should be administered with caution in patients with thyrotoxicosis, phaeochromocytoma, diabetes mellitus, untreated

hypokalaemia, 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. Caution should

be observed when treating patients with prolongation of the QTc-interval. Formoterol itself may induce prolongation of the

QTc-interval. The need for, and dose of inhaled corticosteroids should be re-evaluated in patients with active or quiescent

pulmonary tuberculosis, fungal and viral infections in the airways.

Potentially serious hypokalaemia may result from high doses of beta 2-adrenoceptor agonists. Concomitant treatment of beta 2

adrenoceptor agonists with drugs which can induce hypokalaemia or potentiate a hypokalaemic effect, e.g. xanthine-derivatives,

steroids and diuretics, may add to a possible hypokalaemic effect of the beta 2 adrenoceptor agonist. Particular caution is

recommended in unstable asthma with variable use of rescue bronchodilators, in acute severe asthma as the associated risk may be

augmented by hypoxia and in other conditions when the likelihood for hypokalaemia is increased. It is recommended that serum

potassium levels are monitored during these circumstances. As for all beta 2 adrenoceptor agonists, additional blood glucose

controls should be considered in diabetic patients.

Formatide Inhaler contains lactose monohydrate (<1 mg/inhalation). This amount does not normally cause problems in lactose

intolerant people. The excipient lactose contains small amounts of milk proteins, which may cause allergic reactions.

Drug Interaction with other medicinal products and other forms of interaction:

Pharmacokinetic interactions: Potent inhibitors of CYP3A4 (eg, ketoconazole, itraconazole, voriconazole, posaconazole,

clarithromycin, telithromycin, nefazodone and HIV protease inhibitors) are likely to markedly increase plasma levels of budesonide

and concomitant use should be avoided. If this is not possible the time interval between administration of the inhibitor and

budesonide should be as long as possible. In patients using potent CYP3A4 inhibitors, Formatide maintenance and reliever therapy

is not recommended. The potent CYP3A4 inhibitor ketoconazole, 200 mg once daily, increased plasma levels of concomitantly orally

administered budesonide (single dose of 3 mg) on average six-fold. When ketoconazole was administered 12 hours after budesonide

the concentration was on average increased only three-fold showing that separation of the administration times can reduce the

increase in plasma levels. Limited data about this interaction for high-dose inhaled budesonide indicates that marked increase in

plasma levels (on average four fold) may occur if itraconazole, 200 mg once daily, is administered concomitantly with inhaled

budesonide (single dose of 1000 mcg).

Pharmacodynamic interactions: Beta-adrenergic blockers can weaken or inhibit the effect of formoterol. Formatide should therefore

not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons.Concomitant

treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase inhibitors

and tricyclic antidepressants can prolong the QTc-interval and increase the risk of ventricular arrhythmias.

In addition L-Dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta 2-sympathomimetics. Concomitant

treatment with monoamine oxidase inhibitors, including agents with similar properties such as furazolidone and procarbazine, may

precipitate hypertensive reactions. There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with

halogenated hydrocarbons. Concomitant use of other beta-adrenergic drugs or anticholinergic drugs can have a potentially additive

bronchodilating effect. Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis

glycosides.

Budesonide and formoterol have not been observed to interact with any other drugs used in the treatment of asthma.

Pregnancy and lactation: For Formatide or the concomitant treatment with formoterol and budesonide, no clinical data on exposed

pregnancies are available. 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. Data on approximately 2000 exposed

pregnancies indicate no increased teratogenic risk associated with the use of inhaled budesonide. In animal studies

glucocorticosteroids have been shown to induce malformations. This is not likely to be relevant for humans given recommended

doses.

During pregnancy, Formatide should only be used when the benefits outweigh the potential risks. The lowest effective dose of

budesonide needed to maintain adequate asthma control should be used.

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 Formatide 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.

Side effects: Since Formatide contains both budesonide and formoterol, the same pattern of undesirable effects as reported for

these substances may occur. No increased incidence of adverse reactions has been seen following concurrent administration of the

two compounds. The most common drug related adverse reactions are pharmacologically predictable side-effects of beta 2

adrenoceptor agonist therapy, such as tremor and palpitations. These tend to be mild and usually disappear within a few days of

treatment. Adverse reactions, which have been associated with budesonide or formoterol, are given below, listed by system organ

class and frequency.Frequency are defined as: very common (=1/10), common (=1/100 to <1/10), uncommon (=1/1000 to <1/100), rare

(=1/10 000 to <1/1000) and very rare (<1/10 000).

Formatide Box [https://unimedunihealth.com/wp-content/uploads/2017/05/Formatide-Box-162x300.jpg]

[https://unimedunihealth.com/wp-content/uploads/2017/05/Formatide-Box.jpg]

Candida infection in the oropharynx is due to drug deposition. Advising the patient to rinse the mouth out with water after each

dose will minimize the risk. Oropharyngeal Candida infection usually responds to topical anti-fungal treatment without the need to

discontinue the inhaled corticosteroid.

As with other inhalation therapy, paradoxical bronchospasm may occur very rarely, affecting less than 1 in 10,000 people, with an

immediate increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm responds to a rapid-acting inhaled

bronchodilator and should be treated straightaway. Formatide should be discontinued immediately, the patient should be assessed

and an alternative therapy instituted if necessary.

Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects

are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s Syndrome, Cushingoid

features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and

glaucoma. Increased susceptibility to infections and impairment of the ability to adapt to stress may also occur. Effects are

probably dependent on dose, exposure time, concomitant and previous steroid exposure and individual sensitivity.

Treatment with beta 2 adrenoceptor agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and

ketone bodies.

Overdose: An overdose of formoterol would likely lead to effects that are typical for beta 2 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 over dosage 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.

If Formatide therapy has to be withdrawn due to overdose of the formoterol component of the drug, provision of appropriate inhaled

corticosteroid therapy must be considered.

Pharmaceutical precautions

Store in a cool and dry place, protected from light.

Packaging Quantities

Formatide 4.5/80 HFA: Each canister contains 120 metered dose.

Formatide 4.5/160 HFA: Each canister contains 120 metered dose.

Manufactured by

UniMed&UniHealth Manufacturers Ltd.

B K Bari, Gazipur, Bangladesh

® Registered Trademark