My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I review the NICE guidance on inhalers, both for asthma and COPD. I have summarised the guidance from a Primary Care perspective and I have put the links to that guidance below.

By way of disclaimer, I am not giving medical advice; this video is intended for health care professionals, it is only my interpretation of the guidelines and you must use your clinical judgement.   

There is a YouTube version of this and other videos that you can access here: 

• The NICE GP YouTube Channel: 

https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw  

The following NICE guidance can be found here:

·      Asthma Inhaled corticosteroids- Last revised in April 2022: https://cks.nice.org.uk/topics/asthma/prescribing-information/inhaled-corticosteroids/

·      Asthma: Beta2 agonists- Last revised in April 2022: https://cks.nice.org.uk/topics/asthma/prescribing-information/beta-2-agonists/

·      Chronic obstructive pulmonary disease: Inhaled corticosteroids- Last revised in June 2023: https://cks.nice.org.uk/topics/chronic-obstructive-pulmonary-disease/prescribing-information/inhaled-corticosteroids/

·      Chronic obstructive pulmonary disease: Muscarinic antagonists- Last revised in June 2023: https://cks.nice.org.uk/topics/chronic-obstructive-pulmonary-disease/prescribing-information/muscarinic-antagonists/

·      Chronic obstructive pulmonary disease: Beta-2 agonists- Last revised in June 2023: https://cks.nice.org.uk/topics/chronic-obstructive-pulmonary-disease/prescribing-information/beta-2-agonists/

·      Corticosteroids - inhaled: Scenario: Corticosteroids – inhaled- Last revised in May 2020: https://cks.nice.org.uk/topics/corticosteroids-inhaled/management/corticosteroids-inhaled/#choosing-a-delivery-system

·      Corticosteroids – inhaled- Last revised in May 2020: https://cks.nice.org.uk/topics/corticosteroids-inhaled/

·      Corticosteroids - inhaled: Which inhaled corticosteroids are available in the UK?- Last revised in May 2020: https://cks.nice.org.uk/topics/corticosteroids-inhaled/background-information/types-of-inhaled-corticosteroids/

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Transcript 

Hello everyone, and welcome! I'm Fernando Florido, a GP in the United Kingdom.

Today, we're going to talk about inhalers – those small but powerful things that are a lifeline for people with asthma and COPD. But in the world of inhalers, things can get quite complex. With a multitude of brand names and different devices, navigating this world can feel like getting lost in a maze.

We'll try to bring order to this labyrinth by reviewing the NICE guidance on inhalers, both for asthma and COPD. I have summarised the guidance from a Primary Care perspective and I have put the links to that guidance in the episode description.

But before we begin, let's address the elephant in the room. Memorising the vast array of brand names, combinations, and different devices is no easy task. Not only would it be an overwhelming challenge, but it would also consume valuable brainpower that would be better utilised in other areas of our lives.

So, here's my advice: it's absolutely okay to look up specific inhaler brands when you need to. In today's digital age, we can quickly find the information we need without wasting our mental energy on trying to remember everything. This frees up our minds to focus on what truly matters.

If you prefer a video format, there’s also a YouTube version of these episodes. The link is in the episode description.

Please note that this is my interpretation of the guidelines, not medical advice.

So, with that said, hit that subscribe button and let's dive in!

The video has four parts, inhaled corticosteroids, inhaled beta-agonists, inhaled antimuscarinic agents and combination inhalers. 

Let’s start with inhaled steroids both for asthma and COPD.

What should we consider when initiating inhaled corticosteroids?

We should avoid prescribing generic inhalers to ensure continuity of the device type in future. 

The various inhaled corticosteroids are similar in efficacy and adverse effect profile. However, we need to remember that:

Qvar and Kelhale products have extrafine beclomethasone particles and are twice as potent as other beclometasone inhalers. 

What delivery systems are available for inhaled corticosteroids?

First, we have Pressurized metered-dose inhalers (pMDIs) which use propellant and have an environmental impact.

We also have Spacer devices with pMDIs, which are the preferred option for children under 5

Then we have the Dry powder inhalers (DPIs) which do not use propellant but require enough inspiratory effort to breathe in the powder

We also have the Breath-actuated MDIs (BA-MDIs) which also require sufficient inspiratory effort to activate the device. 

Finally, Nebulizers given as an aerosol that can be inhaled through a mask or mouthpiece. A mouthpiece is preferable to avoid adverse effects caused by exposure to the skin and eyes. 

What contraindications and cautions are associated with inhaled corticosteroids?

There are no contraindications to the use of inhaled corticosteroids and they can be given during pregnancy and breastfeeding.

Cautions are untreated tuberculosis, fungal, bacterial, parasitic, or systemic viral infections, as well as ocular herpes simplex.

What are the effects of inhaled corticosteroids?

Well, they have potent anti-inflammatory activity both the immediate and late phases of asthma.

Inhaled corticosteroids available in the UK include beclometasone, budesonide, ciclesonide, fluticasone, and mometasone.

They are also available as combination inhalers containing long-acting beta-2 agonists.

In asthma, a long-acting bronchodilator should be given in combination with an ICS. In other words, a long-acting bronchodilator should not be normally given in isolation for asthma.

Conversely, in COPD, an ICS should be given in combination with a long-acting bronchodilator, having discussed the risk of adverse effects including an increased risk of pneumonia which may require hospitalization. In other words, an ICS should not be normally given in isolation for COPD.

Local adverse effects include:

Oral candidiasis, sore mouth, dysphonia, and hoarseness, especially in high doses as well as

Paradoxical bronchospasm.

Systemic adverse effects are rare but may occur if high doses are prescribed for prolonged periods.

We will issue a steroid treatment card to:

People using prolonged high doses.

People taking drugs that inhibit steroid metabolism such as antiretroviral HIV drugs

In children, height should be monitored regularly.

And we will use the lowest dose of inhaled corticosteroid (ICS) that maintains effective control of symptoms. 

Which inhaled corticosteroids are available in the UK?

If we want to give Beclometasone dipropionate we can prescribe one of the following brands:

Clenil Modulite MDI

Easyhaler beclometasone

Kelhale MDI

QVAR MDI

QVAR Autohaler

QVAR Easi-Breathe

Soprobec MDI and

Beclu MDI

But we need to be aware that kelhale and Qvar contain beclomethasone extrafine particles and are therefore more potent.

If we want to give budesonide we will prescribe one of the following brands:

Budelin Novolizer

Easyhaler Budesonide and

Pulmicort Turbohaler

If we want to give Ciclesonide we will prescribe: Alvesco MDI

If we want to give Fluticasone we will prescribe Flixotide either the Evohaler MDI or the Accuhaler

And If we want to give Mometasone we will prescribe: Asmanex Twisthaler

What dosing regimens should we consider?

NICE has issued the following guidance on ICS dosages:

A high dose is more than 800 micrograms budesonide or equivalent in adults and more than 400 mcg in children.

A moderate dose is between 400 micrograms and 800 micrograms budesonide or equivalent in adults and between 200mcg and 400 mcg in children

A low dose is 400 micrograms or less of budesonide or equivalent in adults or 200 mcg or less in children.

Examples of dose equivalence are as follows:

Budesonide 200mcg would be equivalent to 200mcg of mometasone and 200 mcg Beclomethasone, but only 100 mcg if we prescribe Beclomethasone extrafine particles.

Equally Budesonide 200mcg would be more or less equivalent to 160 mcg of Ciclesonide or 125 mcg of Fluticasone

Let’s now move on to the section on beta agonists.

By way of introduction, we will say that

Beta-2 agonists — act directly on beta-2 receptors, causing smooth muscle relaxation and dilatation of the airways.

Short-acting beta-2 agonists or SABAs, such as salbutamol and terbutaline, have a rapid onset of action, about 15 minutes and their effects last for up to 4 hours.

Long-acting beta-2 agonists (LABAs) have prolonged receptor occupancy and

Salmeterol and formoterol have a duration of action of 12 hours and

In asthma they should only be used with an ICS.

Indacaterol and olodaterol are once daily LABAs licensed for use in COPD in adults; they are not indicated for the relief of acute bronchospasm.

Vilanterol is available only in combination with fluticasone furoate or/and with the antimuscarinic umeclidinium.

(Cautions)

Beta-2 agonists should be used with caution in people with:

Hyperthyroidism as they may stimulate thyroid activity.

Cardiovascular disease (including hypertension) because of changes to blood pressure and heart rate and an increased risk of arrhythmias especially if there is susceptibility to QT-interval prolongation.

Hypokalaemia, as this may be caused by high doses of beta-2 agonists and

Convulsive disorders.

(Adverse effects)

Adverse effects of short-acting and long-acting beta-2 agonists are similar. They are usually dose related and include:

Nervous system disorders such as tremor, headache, dizziness and seizures.

Cardiac disorders such as palpitations, arrhythmias, peripheral vasodilation and myocardial ischaemia.

Psychiatric disorders such as anxiety, restlessness and insomnia.

Metabolic disorders such as:

Hypokalaemia and

Hyperglycaemia.

Respiratory disorders such as oropharyngeal irritation and paradoxical bronchospasm (which is rare).

Musculoskeletal disorders such as muscle cramps, and

Acute angle-closure glaucoma which has been reported in people using nebulized short-acting beta-2 agonists: using a mouthpiece rather than a mask is preferable to avoid this

We should advise people who are using terbutaline turbohaler to rinse their mouth after each use to minimize systemic absorption.

What drug interactions are important with beta-2 agonists?

Because of the hypokalaemia risk, we should monitor potassium levels with:

Digoxin and

Potassium-depleting drugs like corticosteroids, diuretics, and theophylline

Non-selective B-blocking drugs such as propranolol —and the manufacturer recommends avoid.

And Ketoconazole may increase plasma levels of salmeterol.

Which short-acting beta-2 agonists are available?

Salbutamol is available in the form of:

Airomir autohaler

Airomir MDI

Salamol Easibreathe

Salamol MDI

Ventolin evohaler

Easyhaler salbutamol

Salbulin novolizer

Terbutaline in the form of:

Bricanyl turbohaler              

Which long-acting beta-2 agonists are available?

As we have said before, we can use individual LABA inhalers for COPD.

We have Formoterol:

And Formoterol can be prescribed as:

Atimos modulate

Foradil DPI

Oxis turbohaler

Formoterol Easyhaler.

Then we have Salmeterol:

which can be prescribed as:

Neovent MDI

Serevent evohaler

Serevent accuhaler and

Soltel MDI.

Indacaterol

which can be prescribed as Onbrez Breezhaler

And Olodaterol:

which ca be prescribed as:

Striverdi Respimat

And then we have the combination inhalers, both for asthma and COPD. but we are going to look at them separately in the fourth section of this video.

We are now going to look at the inhaled antimuscarinic agents.

Muscarinic antagonists cause bronchodilation by blocking the bronchoconstrictor effect of acetylcholine on airway smooth muscle.

Ipratropium is a short-acting muscarinic antagonist (or SAMA)

The maximal effect is at 30–60 minutes and

the duration of action is 3–6 hours.

Long-acting muscarinic antagonists (or LAMAs) have a prolonged bronchodilator effect. Examples are:

Tiotropium and also

Aclidinium, glycopyrronium, and umeclidinium.

Which short-acting muscarinic antagonists are available for COPD?

Excluding the preparations for nebulisers

we only have Ipratropium MDI

Which long-acting muscarinic antagonists are available for COPD?

Tiotropium: can be prescribed as:

Spiriva Respimat®

Spiriva® inhalation powder

Acopair inhalation powder,

Tiogiva inhalation powder,

Braltus® inhalation powder,

Aclidinium can be prescribed as:

Eklira inhalation powder

Glycopyrronium can be prescribed as:

Seebri Breezhaler, inhalation powder

And Umeclidinium can be prescribed as:

Incruse Ellipta DPI

When should antimuscarinics be used with caution?

Antimuscarinics should be used with caution in:

Prostatic hyperplasia and bladder-outflow obstruction

Renal impairment

Angle-closure glaucoma especially with nebulizer

And Pregnancy or breastfeeding

Additionally, Tiotropium should be used with caution in people with cardiac arrhythmias, heart failure or myocardial infarction in the previous 6 months because there is an

Increased risk of all-cause mortality following the use of this product.

Lastly, Combination ipratropium with salbutamol is contraindicated in people with hypertrophic obstructive cardio- myopathy or tachyarrhythmia.

What are the adverse effects of antimuscarinics?

The adverse effects of antimuscarinics include:

Cardiac disorders such as arrhythmias and palpitations.

Respiratory disorders such as paradoxical bronchospasm, throat irritation, and cough.

Gastrointestinal disorders such as dry mouth, abnormal taste, nausea, vomiting, constipation and diarrhoea.

ENT disorders such as nasal congestion, dryness of nasal mucosa, and epistaxis.

Nervous system disorders such as headache and dizziness.

Urinary disorders such as bladder outflow obstruction and prostatic hyperplasia.

And Visual disorders including acute angle-closure glaucoma

What drug interactions are important with muscarinic antagonists?

Concurrent use of inhaled antimuscarinics with other antimuscarinic drugs is not recommended as the effects of concurrent use have not been studied.

We now move to look at combination inhalers and

There are three types of combination inhalers

Combination of an ICS with a LABA

which can be used in both asthma and COPD

Combination of three drugs, an ICS, a LAMA and a LABA for use in COPD

Combination of a LAMA and a LABA, that is, without an ICS, for use in COPD

So, What ICS and LABA combination inhalers are available?

We have the following combinations:

Beclometasone and formoterol both as pMDI and DPI: They include

Fostair pMDI

Fostair NEXThaler and

Luforbec pMDI

We need to be aware that Fostair and Luforbec contain extra fine beclomethasone and therefore it is more potent than traditional beclometasone CFC-free inhalers so their dose should be lower.

The combination of Budesonide and formoterol come only as DPI: in the form of

DuoResp Spiromax

Symbicort Turbohaler

Fobumix Easyhaler and

WockAIR DPI

Then we have Fluticasone and formoterol both as pMDI and DPI: in the form of

Flutiform MDI

Flutiform K-haler

The biggest group belong to the Fluticasone and salmeterol combination, both as pMDI and DPI: There are 15 different inhalers such as:

o  Avenor MDI

o  AirFluSal Forspiro 

o  AirFluSal pMDI 

o  Aloflute pMDI 

o  Campona Airmaster

o  Combisal pMDI 

o  Fixkoh Airmaster

o  Fusacomb Easyhaler 

o  Sereflo pMDI 

o  Sereflo Ciphaler

o  Seretide Accuhaler

o  Seretide Evohaler

o  Sirdupla pMDI

Stalpex DPI

Seffalair Spiromax

And on the other extreme, we have just one inhaler for the Fluticasone and vilanterol combination, which is a DPI: which is

Relvar Ellipta

Next question is What ICS, LABA and LAMA combination inhalers are available? And we have 3 groups:

First, we have the Beclomethasone, glycopyrronium and formoterol combination both as pMDI and DPI: and they are

Trimbow pMDI and

Trimbow NEXThaler

Then we have the combination of Budesonide, glycopyrronium and Formoterol as an pMDI: which is

Trixeo MDI

And as the third group, we have Fluticasone, umeclidinium and Vilanterol as a DPI in the form of

Trelegy Ellipta

Finally, What LABA and LAMA combination inhalers are available?

There are four:

Glycopyrronium with formoterol as an MDI in the form of

Bevespi Aerosphere

Glycopyrronium and indacaterol as a DPI in the form of

Ultibro Breezhaler

Then aclidinium with Formoterol as a DPI as

Duaklir

And lastly, tiotropium and olodaterol as an MDI in the form of

Spiolto Respimat

I have checked the NICE guidance and the BNF in order to make this list as exhaustive as possible.

In conclusion, what is important is to know the effect and indications of the different inhaled drugs. Remembering all the different inhaler brands and combinations is tough so it's okay to look them up when you need to saving our brainpower for more important things.

Please keep in mind that this is only a summary and my interpretation of the guidance.

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye