| 1. What is the maximum daily dose of Oxis Turbuhaler? |
| |
| If required, additional actuations above those prescribed for regular maintenance therapy may be used for relief of symptoms up to a maximum total daily dose of 54 µg, including any maintenance dose. However, frequent use, which is more than twice daily and/or more than 2 days per week, of doses above normal maintenance treatment is a sign of sub-optimal asthma control, so treatment should be reassessed in these circumstances. These recommendations are well within the safety margin of the preparation. See prescribing information for further information. |
| |
| 2. What are the potential unwanted systemic effects of Oxis? |
| |
| Oxis Turbuhaler® is very well tolerated in the normal dose range 4.5-36 µg/day (see prescribing information). In excessive doses formoterol, like any ß2-agonist, may cause headache, palpitations and tremor, and less commonly other side effects including hypokalaemia. Such side-effects can be investigated by subjective monitoring of symptoms and by objective measurements of serum potassium level and of the QTc-interval in the electrocardiogram. They are very unusual at normal therapeutic doses. |
| |
| 3. What is the duration of the systemic effects of Oxis? |
| |
inhalation or absorption from the gut have a similar time-course to those of short-acting ß2-agonists, (references 11, 12) and a shorter duration than the systemic effects of salmeterol.(reference 13) Alone amongst ß2-agonists, inhaled formoterol (Oxis) is long-acting in the airways, but short-acting systemically (see figure below).
Oxis is long-acting in the airways and short-acting systemically. The duration of the systemic effects of Oxis is similar to that of short-acting ß2-agonists such as terbutaline and salbutamol (schematic representation, based on clinical studies).(references 8, 11, 12,14, 15) Thus Oxis minimises the systemic burden of long-acting ß2-agonist therapy. |
| |
| 4. How do the safety, tolerability and risks of overdose with Oxis compare with those of short acting ß2-agonists? |
| |
Oxis Turbuhaler® has lower systemic ß2-agonist activity than salbutamol pMDI, (reference 25) when used in doses achieving comparable bronchodilator effects. Oxis Turbuhaler® also induces a lower level of systemic effects than terbutaline Turbuhaler (Bricanyl) (see figure below).(reference 19)
Studies with high doses of Oxis have shown good tolerability. For example, one study showed no significant adverse effects from the inhalation of up to 90 µg (20 inhalations of Oxis Turbuhaler 4.5 µg) over 3 hours in acute asthma. (reference 19) Another study in patients with stable asthma showed no safety problems resulted from the inhalation of a total daily dose of 90 µg for 3 consecutive days. reference 11 The inhalation of a total dose of 54 µg from Oxis Turbuhaler® on a single occasion had no significant adverse effects.(reference 12)
There is no clinical experience of the effects or management of doses above these levels. Tremor, headache, palpitations and tachycardia are likely outcomes, and supportive and symptomatic treatment could be needed in severe cases. However, the risks with Oxis are likely to be no greater than those with conventional short-acting inhaled ß2-agonists such as salbutamol and terbutaline, because Oxis is short-acting systemically despite its prolonged action in the airways.
Oxis has lower systemic ß2-agonist activity than terbutaline (Bricanyl), as shown here by the effect on pulse rate of 20 inhalations of Oxis Turbuhaler, 4.5 µg (total dose 90 µg) and terbutaline Turbuhaler® , 0.5 mg (Bricanyl, total dose 10 mg) administered for the treatment of acute asthma. The patients also received intravenous methylprednisolone, 40 mg, 90 minutes after the first inhaled ß2-agonist dose. The two inhaled drugs had similar effects on FEV1. (Reference 19) |
| |
| 5. Is the development of tolerance a problem with long term Oxis use? |
| |
| Oxis, like all ß2-agonist therapy, has two related but distinct effects: a direct bronchodilating effect and a protective effect against the effects of bronchoconstrictor stimuli. The FACET study showed that the bronchodilating effect of Oxis was maintained over a 12 month period,(reference 3) confirming the results of an earlier 6-month study.(reference 2) The protective effect of Oxis against bronchoconstrictor stimuli, like that of other ß2-agonists, decreases slightly over time, but the remaining protective effect is still clinically significant.(reference 26) |
| |
| 6. Is there a risk that Oxis may put patients at risk by masking worsening of airway inflammation or the development of asthma exacerbations? |
| |
No. Oxis is only currently recommended for use in patients who are also receiving an inhaled steroid. Evidence from a subgroup of the patients in the FACET study showed no evidence of masking worsening of airway inflammation when Oxis therapy is accompanied by inhaled steroid therapy.(reference 27) When exacerbations occurred in patients in FACET, they had the same time-course and severity as those in patients not receiving Oxis (see figure below).(reference 28). The reduced number of exacerbations in the Oxis groups in FACET (reference 3) and in a recent study of Oxis used on as needed basis (reference 20) suggest that Oxis could even aid the improved control of airway inflammation in asthma.
Regular treatment with Oxis in addition to inhaled corticosteroids does not mask the development of an asthma exacerbation. Change in PEF (percent fall from day - 14) over the 14 days before and 14 days after a severe exacerbation in the FACET study (reference 28). |
| |
back to top 
|
