The majority of medications formulated as a capsule are designed to be swallowed, so it is not inconceivable that patients or health care providers may be confused when presented with an inhaler that includes a capsule component. Inhaled medications may be used to treat a range of lung diseases including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Over recent years, numerous new drugs or drug combinations for inhalation have been released into the Australian market and listed on the Pharmaceutical Benefits Scheme (PBS). Table 1 below lists the products currently registered in Australia that are formulated as a capsule that must be inserted into a specifically-designed device prior to inhalation.
Table 1. Currently available capsules for inhalation
Generally, inhalers featuring capsules require the user to remove a capsule from blister packaging and insert it into the device. The capsule is then pierced by activating a button on the device which enables the medication to be removed from the capsule by the inspiratory force of the breath of the user. The empty capsule is then discarded from the device, ready for a new capsule to be inserted when necessary.
The inhaler devices themselves are durable and often only require replacing each time the prescription is renewed, or in some cases less frequently. Novartis provides a new Breezhaler® or Aerolizer® device in the box with each supply of their capsules for inhalation. Tobi® capsules are supplied with five Podhaler® devices per 28-day pack and a fresh device should be used every seven days. Other products, such as Spiriva®, distribute the capsules and the inhalers separately and it is recommended that the inhaler device be replaced every twelve months. It is important to be aware of whether a device is included with the capsules or if it is supplied separately to ensure that a patient does possess an inhaler and that it is in a condition appropriate for use.
It is very important that the appropriate inhaler is supplied on initiation of a capsule-based inhaler for a number of reasons, including:
- To enable demonstration and education if necessary;
- To make the device available to the patient for use with the supplied capsules;
- To prompt the patient’s memory that the capsules should be inhaled, not swallowed; and
- To ensure that the patient is using the correct inhaler device.
As can be seen in Table 1, there are multiple types of devices available to be used with capsules for inhalation. These are designed by the manufacturer for their specific product, and it is not recommended that a different device should be used other than what is specified in the product information. Devices are not considered ‘interchangeable’. Whilst Novartis’ Breezhaler® devices are all similar in design, these devices are branded with the relevant brand name (i.e. Seebri® Breezhaler®, Ultibro® Breezhaler® and Onbrez® Breezhaler®) and are not intended to be used interchangeably. It may be confusing to the consumer if a different branded inhaler was used with their capsules.
Whilst patient (and/or carer) counselling and understanding are imperative for proper use of these devices, even patients who have had adequate education regarding these formulations can experience difficulties. In one recent instance, a nurse contacted the pharmacy department to ask whether there was any monitoring or action required as her patient had just swallowed her Spiriva® capsule. Further questioning revealed that the patient had used Spiriva® correctly for years, but on this particular occasion had gotten confused and swallowed the capsule rather than inhaling its contents via the Handihaler® device. The patient reported the error to the nurse with amusement after having self-administered the capsule incorrectly, telling the nurse ‘in all these years, I’ve never done that before.’
Statistics are lacking to identify the frequency of incorrect route of administration for capsules that are intended for inhalation. A search of the Database of Adverse Event Notifications – medicines on the Therapeutic Goods Administration (TGA) website revealed that between 1971 and January 2017 there were only four cases in which the ‘incorrect route’ of drug administration had been reported for Spiriva capsules. Although this may not seem very frequent, it is possible that this scenario may not be identified as an ‘adverse event’ by those aware of the error. Also, the patient or caregiver may not wish to report the error for fear of embarrassment. As such, it is highly likely that the incidence of administration of Spiriva® via an incorrect route is under reported.
Generally, ingesting capsules intended for inhalation does not result in harm, particularly if only a single dose is ingested. For example, tiotropium and glycopyrronium have low oral bioavailability of around 2–3% and 5% respectively, and are unlikely to cause toxicity. β2 agonists have a higher bioavailability; the product information for Foradile® (eformoterol) for example indicates that ‘the absorption of an oral dose of 80 micrograms is 65% or more, although 70% of this dose undergoes pre-systemic or first pass metabolism.’ Ingesting capsules that contain a β2 agonist may lead to an increased incidence of systemic side effects associated with β2 agonists such as nausea, vomiting, tachycardia, arrhythmias, tremor, hypokalaemia, hyperglycaemia or lactic acidosis. If a tobramycin capsule is ingested, toxicity is unlikely as it also has very poor bioavailability.
Harm from swallowing the capsules may primarily result from a deterioration of a patient’s lung disease symptoms or a delayed onset of effect, since these formulations are most effective when inhaled. It has been suggested that if a patient is not improving with treatment including a capsule for inhalation, they should be queried about whether they are inhaling the contents of the capsule using the inhaler device or if they are swallowing it.
It is worth mentioning that some capsules for inhalation may resemble other capsules that the patient may be prescribed. For instance, a Spiriva® capsule can resemble many brands of cephalexin or meloxicam capsules due to similar colouring. This may lead to accidental ingestion by a consumer, particularly if they have poor eyesight or cognition, or accidental administration by a care giver who may not realise the patient uses an inhaled capsule or is not familiar with how it should be administered.
Conversely, an ISMP Canada Safety Bulletin published in 2009 describes reports of consumers placing the wrong capsule into their Handihaler® and inhaling the contents due to similar capsule appearance. This poses a risk to the patient as the medicine is unlikely to have been formulated for inhalation and may contain excipients or irritants that could result in damage to the lungs or harm to the patient.
Adding further potential confusion for consumers, there are some drugs that must be swallowed to be effective for treating lung disease or acute exacerbations of lung disease. Such medications include steroids (such as prednisolone), theophylline, or montelukast. If a patient had taken such medications prior to the initiation of a capsule for inhalation, they may assume that the capsule must be swallowed rather than inhaled.
Some recommendations that have been suggested to reduce the likelihood of inadvertent oral ingestion of capsules for inhalation include:
- Store capsules for inhalation in their original packaging until ready to use them, and preferably with the appropriate inhaler for the capsules. Storing the capsules with the inhaler may serve as a prompt and assist in preventing a patient or caregiver administering the capsules orally by mistake.
- Advise patients to store their inhaler and capsules for inhalation separately from medicines that are taken orally.
- Institutions storing patient’s medicines may consider labelling the device itself, as well as the box of capsules, so that if the device gets misplaced or separated from the capsules it can be promptly returned to the owner once located.
- Do not place capsules in a dosette box or pill cup with medicines that are intended to be swallowed.
- Packaging should be clearly labelled with thorough instructions to reduce patient or carer confusion. ‘Inhale ONE capsule daily’ may not be sufficiently clear for a patient, and it would be better to state ‘Inhale the contents of ONE capsule using the supplied inhaler daily. FOR INHALATION ONLY.’ Pharmacies may consider including a shortcut for specific inhaled capsules to ensure adequate, efficient, and consistent labelling.
- Do not assume that all capsules should be swallowed, always read the label and consumer medicines information carefully before taking or administering capsules. Ask your pharmacist if you have any questions or are confused.
As a wider range of drugs formulated as capsules for inhalation increases, so too might consumer awareness and familiarity with capsules being administered via a variety of routes. It is of paramount importance that consumers and caregivers are educated in order to minimise confusion and incorrect administration of such capsules.
- Rossi S, ed. Australian Medicines Handbook, 2017. Adelaide: Australian Medicines Handbook Pty Ltd, 2017.
- Respiratory Expert Group. Inhalational drug delivery devices [revised 2015 March]. In: eTG complete [Online]. Melbourne: Therapeutic Guidelines Limited; 2017.
- Seebri® Breezhaler® (glycopyrronium [as bromide]) Australian approved product information. Macquarie Park: Novartis Pharmaceuticals Australia Pty Limited. Approved Aug 2016.
- Ultibro® Breezhaler® (indacaterol; glycopyrronium) Australian approved product information. Macquarie Park: Novartis Pharmaceuticals Australia Pty Limited. Approved Nov 2016.
- Onbrez® Breezhaler® (indacaterol) Australian approved product information. Macquarie Park: Novartis Pharmaceuticals Australia Pty Limited. Approved Feb 2014.
- Foradile® (formoterol [eformoterol] fumarate dihydrate) Australian approved product information. Macquarie Park: Novartis Pharmaceuticals Australia Pty Limited. Approved Nov 2016.
- Tobi® (tobramycin) Australian approved product information. Macquarie Park: Novartis Pharmaceuticals Australia Pty Limited. Approved 22 Jun 2015.
- Spiriva (tiotropium bromide) Australian approved product information. North Ryde: Boehringer Inhelheim Pty Limited. Approved 13 September 2016.
- Australian Government. Department of Health. Therapeutic Goods Administration [Internet]. ACT: Therapeutic Goods Administration; 2017. Database of Adverse Event Notifications – medicines; [updated 2017 Jan 20; cited 2017 May 1].
- Institute for Safe Medication Practices Canada. ISMP Canada Safety Bulletin. Volume 9, Number 10; 2009.
- Institute for Safe Medication Practices Canada. Some Capsules Are Not Meant to be Swallowed. Health Canada, 2013.
- Tezky T, Holquist C. FDA Safety Page: Misadministration of capsules for inhalation. Drug Topics. Modern Medicine Network, 2005.
- Waknine Y. FDA Cautions Against Swallowing Tiotropium and Formoterol Capsules. Medscape [Internet], 2008.
- Kelly, K. Capsules for Inhalation May Be Mistaken for Oral Capsules. Pharmacy Times, 2006.
- Cephalex® (cephalexin) Australian approved product information. Dee Why: Phamacor Pty Limited. Approved September 2015.
- APO-Meloxicam (meloxicam) Australian approved product information. Macquarie Park: Apotex Pty Ltd. Approved 01 September 2016.