3.0 Respiratory

The preferred formulary choice of inhalers containing steroids for managing asthma and COPD with suitable conversion options from a less desirable to a preferred inhaler can be found here. Further information is below.

ASTHMA

For asthma prophylaxis, must be used regularly. Clenil Modulite® or Qvar® are most economical when lower doses are required and should be used first line.  See 'CFC-Free Beclometasone Inhalers' below.    

Risks associated with high dose inhaled corticosteroid (ICS)

The risk of systemic adverse effects from ICS is dose related. For adults, low to moderate doses represent little or no risk but, high-dose therapy has been directly linked to adverse effects such as skin thinning, bruising, osteoporosis, diabetes and adrenal suppression. Patients on high dose ICS should be reviewed regularly and provided with a steroid card.

Approximately 85% of patients with asthma can be controlled on doses ≤800 micrograms/day of ICS.

COPD

Patients with COPD and with an FEV ₁  of less than or equal to 50% of predicted, and having two or more exacerbations per year (requiring antibiotic or oral corticosteroid) should be offered prophylactic treatment with inhaled corticosteroid as a combination with long acting therapy, and review at 8 weeks.

CFC-Free Beclometasone Inhalers

These two CFC-free products (QVAR® and Clenil Modulite®), both containing the active substance beclometasone dipropionate are NOT equipotent and this could have safety implications.  When the prescriber wishes a patient to have a CFC-free formulation of beclometasone dipropionate that intention should be made clear by prescribing the product by brand name.  Pharmacists receiving a generic prescription for a beclometasone dipropionate pMDI must establish which of the two available branded products should be dispensed.

1. Clenil Modulite® (Trinity-Chiesi Pharmaceuticals Limited) should be prescribed at the same dose as the CFC-containing beclometasone dipropionate pMDIs.

2. Qvar® (Ivax Pharmaceuticals Limited) has a 2 to 2.5 fold greater potency than the CFC-containing beclometasone dipropionate pMDIs and therefore should be prescribed at a lower dose than the CFC-containing beclometasone dipropionate pMDIs. Further information is available in the Summary of Product Characteristics.

3. Clenil Modulite® is authorised for use in children; Qvar® is not authorised for use in children (12 years of age and younger).

4. For all inhaled corticosteroids and in line with accepted clinical practice, when control of asthma is achieved the dose of the inhaled corticosteroid should be titrated to the lowest dose at which effective control of asthma is maintained.

All NEW patients requiring a beclometasone inhaler, should be initiated on a CFC-free brand, either QVAR® or Clenil Modulite®.  The choice of brand used should be based on the dose required, the licensed indications, cost and cost effectiveness and the inhaler types available. 

Other Steroid Inhalers

When considering doses, beclometasone dipropionate (Clenil® brand) and budesonide are equipotent and fluticasone is twice as potent. 

GREEN      Budesonide (Pulmicort®)  dry powder inhaler

GREEN      Fluticasone (only recommended when high dose therapy is required).    

Compound preparations containing corticosteroids

If patients remain symptomatic on monotherapy, their treatment should be intensified by combining therapies from different drug classes. Combination of long-acting beta2-agonist plus inhaled steroid is a treatment option. The clinical effectiveness of combined treatments can be assessed by improvements in symptoms, activities of daily living, exercise capacity and lung function. Combination treatment should be discontinued if there is no benefit after 4 weeks.  

DuoResp®, Spiromax®, Fobumix Easyhaler® and Symbicort® Tubohaler containin budesonide/formoterol.

There are 2 strengths of DuoResp® Spiromax and Fobumix Easyhaler®160/4.5, and   320/9 ,These are equivalent to Symbicort 200/6 and Symbicort 400/12 respectively.

Although equivalent the inhaler devices are significantly different. Resultantly it is important to specify theinhaler by brand when prescribing in order to ensure patients receive a device they are familiar with.

                  (dose= 1puff twice daily, max 2 puffs twice daily)           

                 (dose = 1 puffs twice daily, max 2 puffs twice daily) Dose for COPD is 1 puff twice a day

Note: Of the Symbicort® range, both the 200/6 and 400/12 strengths are licensed for use in COPD as are the DuoResp Spiromax.

 Symbicort® SMART, DuoResp Spiromax maintenance and reliever therapy and Fostair® MARTregime for asthma

 Symbicort® and DuoResp Spiromax inhalers contain the inhaled steroid budesonide and the long action beta-2 agonist formoterol whilst Fostair contains ultra fine beclomethasone and formoterol. Although long acting formoterol has a quick onset of action allowing it to be used to relieve symptoms when required..The use of Symbicort® 100/6 or 200/6 used as a rescue medication instead of a short acting beta-2 agonist such as salbutamol in addition to its regular use as a controller therapy has been shown to be an effective treatment regimen. In line with updated BTS Guidance, Symbicort® SMART regimen for use in asthma in adults is approved within the following restrictions:

• In selected adult patients at step 3 of the BTS/NICE guidelines who are poorly controlled, or in selected adult patients at step 2 (above beclometasone 400micrograms/day who are poorly controlled),
• Patients taking rescue Symbicort® once a day or more should have their treatment reviewed,
• Careful patient selection and education of patients about the specific issues around this management strategy is required.

 Only the 100/6 and 200/6 strengths should be used as part of this regimen. The 400/12 strength of Symbicort® should not be used in this way.

DuoResp Spiromax maintenance and reliever therapy- Only the 160/4.5microgram strength should be used as part of this regimen.

Patients take a daily maintenance dose of DuoResp Spiromax and in addition take DuoResp Spiromax as needed in response to symptoms. Patients should be advised to always have DuoResp Spiromax available for rescue use. DuoResp Spiromax maintenance and reliever therapy should especially be considered for patients with:

• inadequate asthma control and in frequent need of a reliever inhaler.

• asthma exacerbations in the past requiring medical intervention.

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.

Fostair® may also be used as maintenance and reliever therapy (MART) It  is currently recommended as an option for the management of asthma in adults in line with BTS guidance. This product is not licensed for use in children or adolescents under the age of 18 years.

(Fostair 100/6 MDI 1 puff twice a day plus extra puffs as required max 8 puffs daily)

Again careful patient selection and education about the specific issues around this management strategy is required.

Fluticasone/Salmeterol inhalers

For 12-18 year olds at Step 3 of the asthma guidelines who cannot use Symbicort Turbohaler, Fostair or Sirdupla are not licensed. The alternative choice therefore is Seretide 50 MDI 2 puffs BD at Step 3a and Seretide 125 2 puffs BD at Step 3b.

NOTE: Of the Seretide® range, only the Seretide® Accuhaler 500 is licensed for use in COPD.

            Neither the Seretide® Evohaler nor the Accuhaler® strengths are licensed for use in COPD. 

3.3.2 Leukotriene receptor antagonists and omalizumab

The leukotriene receptor antagonists block the effects of the cysteinyl leukotrienes in the airways. They are relatively expensive agents and BTS guidelines recommend their addition to therapy only at Step 3 for both adults and children.

Omalizumab  - NICE TA278  (review of NICE TA133 and TA201)

Omalizumab should be initiated and prescribed only by a specialist in the treatment of asthma, and used strictly within its licensed indications.  Omalizumab is licensed as add-on therapy to improve control of asthma control in adults and adolescents 12 years and over and children aged 6 to 11 years with severe persistent allergic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and who have reduced lung function (FEV1<80%) as well as frequent daytime symptoms or night-time awakenings and who have had multiple documented severe asthma exacerbations despite daily high-dose inhaled corticosteroids, plus a long-acting inhaled β2-agonist. Treatment should only be considered for patients with convincing IgE mediated asthma.

Only patients with an IgE level of >30 – 700 IU/ml, and body weight of >20 – 150kg are eligible for treatment.  The dose is determined from the baseline IgE level, see the SPC for details.  It is given subcutaneously, at 2-4 weekly intervals, and response to treatment is measured at 16 weeks.  Only patients who have shown an adequate response to treatment will continue therapy.   

The manufacturer in the USA has been asked by the FDA to add a boxed warning stating that there is a possibility of a patient developing anaphylaxis after any dose, even if there was no reaction to the first dose. In addition, anaphylaxis after administration of the drug may be delayed for up to 24 hours after the dose is given.

Therefore, health care professionals should:

• be prepared to manage life-threatening anaphylaxis following administration of the drug
  
• observe patients foe at least two hours after an injection

be offered and know how to initiate emergency self-treatment for anaphylaxis (Where this is prescribed & patients should know how and when to administer an adrenaline/epinephrine autojector (Epipen®) with their first prescription.

Anaphylaxis was reported in clinical trials at a frequency of approximately one in a thousand patients (0.1%); usually these reactions occurred within 2 hours of an injection. However the agency has received new reports of delayed anaphylaxis (within 2 to 24 hours or even longer) after treatment.

Please note that for children under the age of 6 omalizumab has a BLACK traffic light.

RED           Omalizumab injection 150mg – Risk of anaphylaxis (up to 24hrs after dose) see advice above

Mepolizumab  -NICE TA431

3.4.1 Antihistamines

Adrenaline pre-filled syringes

Note the expiry of Jext ® has been reduced by the manufacturers from 24 months to 18 months.

                   EpiPen® 0.3mg

All material in this section is aimed at health care professionals, but is information currently held in the public domain, members of the  public seeking advice on medicine-related matters are advised to speak with their GP, pharmacist, nurse or contact NHS111 Service.

  Email: info.elmmb@nhs.net

3.5.1 Respiratory stimulants

3.5.2 Respiratory surfactants

RED           Poractant suspension (Curosurf®) 80mg/ml, 1.5ml & 3ml vial

Carbocisteine should be initiated by secondary care respiratory physicians for chronic cough productive of sputum as outlined in NICE guidance. Therapy should only be continued if there is symptomatic improvement e.g. reduction in frequency of cough and sputum production.

•  Dornase alfa is RED Traffic Light where prescribing has been initiated on or after 1st April 2013.

  Where prescribing was initiated prior to April 1st 2013 the traffic light status may remain amber until repatriation of patients has been agreed by NHS England, local commissioners and providers.

Hypertonic sodium chloride

Inhaled hypertonic saline is a widely-used and well-accepted therapy for increasing the mucilliary clearance in the lower airways in patients with cystic fibrosis. Patients especially benefit from sputum expectoration due to osmotic effects of hypertonic saline. Different doses and concentrations are used in common therapy. The DTC has supported the use of this product .The efficacy and tolerability of hypertonic saline has been demonstrated in several clinical trials.

3.11.1  Antifibrotics