Vannair 80:4,5 80 μg, 160 μg Inhaler

Asthma: VANNAIR 80:4,5 & 160:4,5:
VANNAIR is indicated in the treatment of asthma in adults and children 6 years and older where continued use of a combination (inhaled corticosteroid and long-acting beta-2-agonist) is appropriate.
COPD: VANNAIR 160:4,5:
VANNAIR 160:4,5 u03bcg/dose is indicated in the regular treatment of patients with moderate to severe chronic obstructive pulmonary disease (COPD), with frequent symptoms and a history of exacerbations.

The dosage of VANNAIR should be individualised according to disease severity. When control has been achieved, the dose should be titrated to the lowest dose at which effective control of symptoms is maintained. VANNAIR is taken as regular maintenance treatment. Patients should be advised to have their separate rapid-acting bronchodilator available for rescue use at all times. Increasing use of a separate rapid-acting bronchodilator indicates a worsening of the underlying condition and warrants a reassessment of the asthma therapy.

Patient Dosage Recommendation
Asthma in adults and adolescents: VANNAIR 80:4,5 or 160:4,5:
Adults (18 years and older): 2 inhalations twice daily
In some cases, up to a maximum of 4 inhalations twice daily may be required as maintenance dose or temporarily during worsening of asthma.
Adolescents (12-17 years): 2 inhalations twice daily
During worsening of asthma the dose may temporarily be increased to a maximum of 4 inhalations twice daily.
Asthma in children: VANNAIR 80:4,5:
Children (6-11 years): 2 inhalations twice daily
Maximum daily dose: 4 inhalations
COPD: VANNAIR 160:4,5:
Adults (18 years and older): 2 inhalations twice daily
Maximum daily dose: 4 inhalations

General information:
The patients should be instructed that, for optimal benefit VANNAIR must be used even when they are asymptomatic. There are no special dosing requirements for elderly patients. There are no data available for use of VANNAIR 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 diseases.

Instructions for correct use of VANNAIR inhaler:
On actuation of VANNAIR, a volume of the suspension is expelled from the canister at high velocity. When the patient inhales through the mouthpiece at the same time as actuating the inhaler, the substance will follow the inspired air into the airways.

Note: It is important to instruct the patient to:
u2022 Carefully read the instructions for use included at the end of the package insert, which is packed together with each inhaler.
u2022 Shake the inhaler gently prior to each use to mix its contents properly.
u2022 Prime the inhaler by actuating it twice into the air when the inhaler is new, has not been used for more than 1 week or if it has been dropped.
u2022 Place the mouthpiece in the mouth. While breathing slowly and deeply, press the device firmly to release the medication. Continue to breathe in and hold the breath for approximately 10 seconds or as long as is comfortable.
u2022 Shake the inhaler again and repeat.
u2022 Rinse the mouth with water after inhaling the maintenance dose to minimise the risk of oropharyngeal thrush.
u2022 Clean the mouthpiece of the inhaler regularly, at least once a week with a dry clean cloth.
u2022 Do not put the inhaler into water.
u2022 The VANNAIR inhaler must not be taken apart. The VANNAIR canister must only be used with the VANNAIR actuator and, the VANNAIR actuator must not be used with any other inhalation product.

Hypersensitivity (allergy) to budesonide, formoterol or any of the excipients listed in section 6.1

Treatment with VANNAIR should not be initiated to treat a severe exacerbation. It is recommended that the dose be tapered when long-term treatment is discontinued and should not be stopped abruptly. If the patient finds the treatment ineffective, or exceeds the prescribed dose of VANNAIR, 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. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap. Patients should be advised to have their separate rapid-acting bronchodilator available for rescue use at all times. Medical practitioners should closely follow the growth of children and adolescents taking long-term corticosteroids by any route, and weigh the benefits of the corticosteroid therapy against the possible risk of growth suppression. Particular care is needed in patients who are transferred from systemic to inhaled glucocorticosteroids since they may remain at risk of impaired adrenal function for a considerable time. Patients who have required prolonged treatment at the highest recommended dose of inhaled corticosteroids, may also be at risk. These patients may exhibit signs and symptoms of adrenal insufficiency when exposed to surgery and infection or conditions associated with severe electrolyte loss or severe stress. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery. In recommended doses VANNAIR supplies less than normal physiological amounts of glucocorticosteroid systematically and does NOT provide the mineral corticosteroid activity that is necessary for coping with these emergencies.

VANNAIR should be administered with caution in patients with severe cardiovascular disorders (including heart rhythm abnormalities), diabetes mellitus, untreated hypokalaemia or thyrotoxicosis. High doses of beta-2-agonists can lower serum potassium by inducing a re-distribution of potassium from the extracellular to the intracellular compartment, via stimulation of Na + /K + - ATPase in muscle cells. The clinical importance of this effect is uncertain.

Pharmacokinetic interactions:
The metabolism of budesonide is primarily mediated by the enzyme CYP3A4. Inhibitors of this enzyme, e.g. ketoconazole, may therefore increase systemic exposure to budesonide. This is of limited clinical importance for short-term (1-2 weeks) treatment with ketoconazole, but should be taken into consideration during long-term treatment with ketoconazole.

Pharmacodynamic interactions:
Beta-adrenergic blockers (including eye drops) can weaken or inhibit the effect of formoterol. Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines, monoamine oxidase inhibitors and tricyclic antidepressants can prolong the QTc interval and increase the risk of ventricular dysrhythmias. Budesonide and formoterol have not been observed to interact with any other medicine used in the treatment of asthma.

The safety of VANNAIR in pregnant and lactating women has not been established.
Pregnancy
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.
Breastfeeding
Safety in breastfeeding has not been demonstrated. A clinical pharmacology study has shown that inhaled budesonide is excreted in breast milk.

VANNAIR is not expected to adversely affect the ability to drive or use machines.

Tabulated summary of adverse reactions
Since VANNAIR contains both budesonide and formoterol, the same type and intensity of undesirable effects as reported for these substances may occur. The most common medicine related adverse reactions are pharmacologically predictable side effects of beta-2-agonist therapy, such as tremor and palpitations. These tend to be mild and disappear within a few days of treatment.

Adverse reactions which have been associated with budesonide or formoterol are given below in Table 1:
Table 1: Adverse reactions by frequency and system organ class (SOC):
Frequency System Organ Class Event
Common 1 % to 10 %
Cardiac disorders: Palpitations
Infections and infestations: Candida infections in oropharynx, Pneumonia (in COPD patients)
Nervous system disorders: Headache, tremor
Respiratory, thoracic and mediastinal disorders: Irritation in the throat, coughing, hoarseness
Uncommon 0,1 % to 1 %
Cardiac disorders: Tachycardia
Gastrointestinal disorders: Nausea
Musculoskeletal and connective tissue disorders: Muscle cramps
Nervous system disorders: Dizziness
Psychiatric disorders: Agitation, restlessness, nervousness, sleep disturbances
Rare 0,01 % to 0,1 %
Cardiac disorders: Cardiac dysrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystoles
Immune system disorders: Immediate and delayed hypersensitivity reactions, e.g. dermatitis, exanthema, urticaria, pruritus, angioedema and anaphylactic reaction.
Respiratory, thoracic and mediastinal disorders: Bronchospasm
Skin and subcutaneous tissue disorders: Skin bruising
Very rare < 0,01 %
Cardiac disorders: Angina pectoris
Endocrine disorders: Signs or symptoms of systemic glucocorticosteroid effects, e.g. hypofunction of the adrenal gland
Metabolism and nutrition disorders: Hyperglycaemia
Psychiatric disorders: Depression, behavioural disturbances

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

An overdose of formoterol would likely lead to effects that are typical for beta-2-adrenergic agonists: tremor, headache, palpitations, and tachycardia. Hypotension, metabolic acidosis, hypokalaemia and hyperglycaemia may also occur. Supportive and symptomatic treatment may be indicated. A dose of 90 u03bcg administered during 3 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 may appear.