Missed medicine doses: how pharmacists can help

Case scenario

Mrs Johnson, a 65-year-old patient with hypertension, comes to the pharmacy to fill her repeat prescriptions for perindopril 4 mg and amlodipine 5 mg. You notice that Mrs Johnson is getting her repeats dispensed irregularly and offer her a blood pressure (BP) check. Mrs Johnson mentions that her BP has been poorly controlled, and she often forgets to take her medicines.

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Introduction

Missed or delayed administration of prescribed doses is a common concern in clinical practice and can be viewed under the framework of non-adherence, either intentional or unintentional. Medication adherence refers to the extent to which a person’s behaviour matches with the agreed recommendations from a health care provider.¹ Adherence to prescribed dosing regimens is crucial for achieving the best therapeutic outcome.

Understanding the implications of missed doses and how to manage them effectively will assist pharmacists in providing clear and concise instructions to patients who miss a dose.

Terminologies

Different terminologies have been used to describe deviations from prescribed therapies. The terms adherence, compliance and concordance are often used interchangeably. However, compliance implies patient passivity in treatment decisions.²

Adherence and concordance suggest a more active and collaborative approach between the patient and healthcare provider, with concordance specifically highlighting the importance of mutual agreement in treatment decisions.³

Reasons for missed doses

Many underlying factors contribute to an individual’s adherence to their medication regimens. When considering the factors contributing to missed medicine doses, several patient-related aspects are particularly relevant for pharmacists. A patient may deliberately skip or delay a dose due to adverse effects, a perceived lack of effect, a lack of motivation, or if they believe the medicine is unnecessary.⁴ On the other hand, unintentional
missed doses may be due to careless factors, including forgetfulness and limited understanding of the prescribed instructions.⁴

In a survey of patient adherence to medicines for chronic diseases, 60% of participants stated forgetfulness was the reason for missed doses.⁵ The study found that missed doses were more commonly reported by patients with vitamin D deficiency, followed by hyperlipidaemia.⁵

The reasons for missed doses may also be a combination of intentional and unintentional factors. For instance, patients who are not motivated to take a medicine may be more likely to forget to take a dose.⁴

Circumstances leading to missed medicine doses

Missed or delayed medicine doses are more likely when regimens are complex due to forgetfulness or when patients have fears and concerns about adverse drug reactions.⁶ Inadequate communication between healthcare providers and patients can also lead to confusion about medication regimens.⁶ For other individuals, busy schedules, frequent travel, major life events or interruptions to usual routines can disrupt their ability to take medicines consistently.⁷

The World Health Organization identified the following five interacting dimensions that affect medication adherence^8,9:

• Healthcare system – accessibility and quality of healthcare services, including the availability of healthcare professionals, ease of accessing healthcare facilities, and the quality of communication between patients and healthcare providers.
• Socioeconomics – financial aspects and social determinants of health, including income level, education, lifestyle, social support networks and cultural beliefs.
• Medicine-related – the nature of the medicine prescribed, including the complexity of the medication regimen, effects of the medicine, cost involved, and the formulation.
• Condition-related – state of disease control, disease characteristics, presence of comorbidities, and the severity of symptoms.
• Patient-related – patient characteristics such as cognitive function, psychological state, health literacy, personal priorities, or non-modifiable characteristics such as demographics.
• Healthcare professionals should be aware that medicine-taking behaviour
  is extremely complex and requires numerous multifactorial strategies to improve adherence.² 

Time-critical medicines

Time-critical medicines are ‘medicines where early or delayed administration by more than 30 minutes from the prescribed time for administration may cause harm to the patient or compromise the therapeutic effect, resulting in suboptimal therapy’.¹⁰ An example is levodopa-containing products for the treatment of Parkinson’s disease. A short delay can worsen symptoms and cause rigidity, pain and tremor, increase the risk of falls, as well as cause stress, anxiety and difficulty in communicating.^11,12 Additionally, anticoagulants (e.g. enoxaparin) require strict adherence to dosing schedules, as clotting complications such as deep vein thrombosis or pulmonary embolism can be life-threatening.¹³

Identifying whether a medicine is time-critical requires knowledge of the half-life of the medicine, as it is a major determinant of the fluctuation in inter-dose concentrations at a steady state.¹⁴ Half-life serves as guidance for making informed recommendations on what to do when a dose of medicine is missed. Four to five half-lives is a general rule of thumb used to approximate the time needed for a medicine to be considered eliminated from the body. At that time point, the plasma concentrations of a given medicine will reach below a clinically relevant concentration.¹⁵

Possible impact of delayed or missed doses

While an occasional missed dose of most medicines will have little consequence on therapeutic outcomes, delays or omissions for some medicines can lead to serious harm. For some medicines, such as an antidepressant, it is possible to get withdrawal symptoms within hours of the first missed dose.¹⁶

Missing a dose of medicines with a short half-life and/or rapid offset of action in relation to the dosing interval may lead to periods of sub-therapeutic plasma drug concentrations, and therefore insufficient pharmacologic activity.¹⁷ In contrast, medicines with a long half-life stay in the body longer. As a result, missing a dose may not cause a significant drop in drug levels, reducing the risk of sub-therapeutic levels. However, it is important to note that the clinical effects of some medicines are not directly related to their half-lives.¹⁴ Some examples of these drugs are those that act via an irreversible mechanism (e.g. aspirin), an indirect mechanism (e.g. warfarin), and those that are pro-drugs or metabolised into an active form with a different half-life.^14,18

The following are some examples of medicines requiring strict adherence to dosing schedules to avoid significant or catastrophic long-term patient impact:

• Anticoagulants due to possible risk of thrombosis¹³
• Anticonvulsants due to risk of seizure activity, especially if omitted perioperatively or if charted to relieve seizures^13,14
• Antimicrobials due to risk of drug resistance, sepsis, prolonged infection, incorrect interpretation of therapeutic drug monitoring¹³
• Bronchodilators due to risk of breathing issues¹³
• Immunosuppressants due to risk of poor immunosuppressant control and exacerbation of symptoms¹³
• Oral contraceptives due to risk of contraceptive failure^14,21
• Psychotropics due to risk of poor symptom control.^13,14

Steps to take when a dose is missed or delayed

1. Consumer Medicine Information

The first place a patient should be instructed to look for advice if they forget to take a dose of their medicine at the usual time is the Consumer Medicine Information (CMI) leaflet.

Most commonly dispensed medicines have a CMI leaflet with a section for when a dose is missed.¹⁹

Pharmacists should use the CMI to reinforce verbal advice for missed or delayed doses during their counselling as it would prepare patients for this eventuality. Pharmacists should provide approved CMI leaflets to patients when they start prescription medicines, and at each subsequent dispensing according to established guidelines as part of good dispensing practice.¹⁸

CMIs are usually included as part of the medicine packaging. Alternatively,
the TGA website (www.ebs.tga.gov.au) provides access to the latest approved versions of the CMI and Product Information (PI) provided by the pharmaceutical companies for most
of the prescription medicines available in Australia.

2. Other methods

Other ways patients can obtain information about missed medicine doses include²⁰:

• Speaking to their pharmacist
• Calling 1300 MEDICINE on
  1300 633 424 (9 am to 5 pm, Monday to Friday, Australian Eastern Standard Time, excluding public holidays)
• Searching for the CMI in Healthdirect’s medicines section at www.healthdirect.gov.au/medicines
• Searching for the CMI in the NPS MedicineWise Medicine finder at www.nps.org.au/medicine-finder
• Contacting the relevant pharmaceutical company (contact details can generally be found on the company’s Australian website).

3. General advice

When specific information is not available, the general advice to manage a missed or delayed dose is to take the missed dose as soon as it is remembered if the dose is less than 2 hours late.²¹ If the dose is more than 2 hours late²¹:

• For medicines taken once or twice daily, take the missed dose as soon as it is remembered, as long as the next dose is not due within a few hours, then continue taking the medicine at the usual times.
• For medicines taken more often than twice daily, skip the missed dose, wait until the next dose is due, and then continue taking the medicine at the usual times.

4. Do not take a double dose

It is generally not recommended to take a double dose to make up for a forgotten dose unless specifically advised.²¹

Examples of missed dose management

Many medicines have special instructions on managing missed doses. While it is not possible to include advice for all, Table 1 lists a few examples of some common medicines that pharmacists may encounter in their daily practice.

Strategies to prevent a missed or delayed dose

Pharmacists play a central role in preventing a missed or delayed dose. The strategies to avoid missed doses lie within the underlying cause.⁴ In addition to clearly explaining the dosing schedule, pharmacists should also focus on addressing the importance of taking medicine consistently as prescribed, particularly for medicines indicated for asymptomatic conditions or preventive measures, as the benefits may not be realised immediately. One study suggests using strategies such as motivational interviewing or another approach that addresses behavioural intention.⁴

Pharmacists should consider and act on the barriers patients might face in adhering to their medication regimen, which may include forgetfulness, complex or variable dosing schedules, adverse effects, or other health, dexterity or vision issues. This may require considerations of how the patient’s daily routine or lifestyle might impact their ability to take their medicines as prescribed (e.g. work schedule, travel). For instance, patients with cognitive impairment or those who forget to take their medicines may need memory triggers and a way to check whether or not they took them.⁴

Pharmacists can suggest the use of dose administration aids, pill organisers, sticky notes, alarm reminders on mobile phones, or “habit stacking” by associating medicine administration with a daily routine such as mealtimes and keeping the medicine visible.⁵ Some patients may find themselves frequently forgetting if they have taken their medicines, which is common for mundane behavioural decisions. One solution is to create a habit of recording each dose on a calendar, or if it is a pill bottle, simply flip it over every time a dose is taken as a visual reminder. Lastly, consider if alternative formulations (e.g. extended-release or combination formulations) are an option, as this could reduce the frequency of doses, thereby simplifying medication regimens.

Knowledge to practice

Pharmacists can effectively manage missed doses by recommending appropriate action for missed doses and proposing tailored strategies that work best to address a specific barrier for patients. Pharmacists can provide patient education and counselling for medication adherence, collaborate with the patient’s primary care provider to discuss potential adjustments to their treatment plan, as well as offer dose administration aids. These actions can have a substantial impact on patient outcomes, including improved therapeutic outcomes, reduced health complications, improved quality of life and patient empowerment.

Conclusion

Missed medicine doses are common in practice, with potentially serious consequences for patient health, particularly when it comes to time-critical medicines. Pharmacists play a crucial role in providing advice for managing missed doses and supporting patients with their medication regimen management through the various strategies available.

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Key points

• Many underlying factors contribute to an individual’s adherence to their medication regimens.
• A missed or delayed dose of time-critical medicines can cause harm to the patient or compromise the therapeutic effect, resulting in suboptimal therapy.
• Consumer Medicine Information leaflets often provide information on managing missed medicine doses.
• Pharmacists play an important role in preventing missed doses by identifying the underlying cause and suggesting strategies to manage complex medication regimens.

References 

1. Burkhart PV, Sabaté E. Adherence to long-term therapies: evidence for action. J Nurs Scholarsh 2003;35(3):207.
2. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc 2011;86(4):304–14.
3. De Mauri A, Carrera D, Vidali M, et al. Compliance, adherence and concordance differently predict the improvement of uremic and microbial toxins in chronic kidney disease on low protein diet. Nutrients 2022;14(3).
4. Riegel B, Dickson VV. A qualitative secondary data analysis of intentional and unintentional medication nonadherence in adults with chronic heart failure. Heart Lung 2016;45(6):468–74.
5. Altamimi AF, Alqahtani ZA, Almughaiseeb FA, et al. The attitude and prevalence of patient noncompliance toward chronic disease medications in Saudi Arabia. J Family Med Prim Care 2021;10(8):3064–70.
6. Jimmy B, Jose J. Patient medication adherence: measures in daily practice. Oman Med J 2011;26(3):155–9.
7. Atinga RA, Yarney L, Gavu NM. Factors influencing long-term medication non-adherence among diabetes and hypertensive patients in Ghana: a qualitative investigation. PLoS One 2018;13(3):e0193995.
8. Peh KQE, Kwan YH, Goh H, et al. An adaptable framework for factors contributing to medication adherence: results from a systematic review of 102 conceptual frameworks. Journal of Gen Int Med 2021;36(9):2784–95.
9. World Health Organization. Adherence to long-term therapies:evidence for action. Geneva: WHO; 2003.
10. Government of Western Australia Department of Health. Guiding principles for timely administration of medications. 2020. At: www.health.wa.gov.au/~/media/Files/Corporate/Policy-Frameworks/Clinical-Governance-Safety-and-Quality/Policy/High-Risk-Medication-Policy/Supporting/Guiding-Principles-for-Timely-Administration-of-Medications.pdf
11. Yu JRT, Sokola BS, Walter BL. Optimization of inpatient medication administration among persons with Parkinson’s disease: recommendations on pharmacy technology and workflow. Front Pharmacol 2023;14:1254757.
12. Rossi S, ed. Other drugs for Parkinson’s disease. Adelaide: Australian Medicines Handbook Pty Ltd; 2024.
13. Anderson E, Prior F. Which medicines are ‘time-critical’? The Society of Hospital Pharmacists of Australia 2020;2(1).
14. Gilbert A, Roughead L, Sansom L. I’ve missed a dose; what should I do? Australian prescriber 2002;25(1):16–8.
15. Hallare J, Gerriets V. Half Life. StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.
16. Warner CH, Bobo W, Warner C, et al. Antidepressant discontinuation syndrome. Am Fam Physician. 2006;74(3):449–56.
17. Albassam A, Hughes DA. What should patients do if they miss a dose? A systematic review of patient information leaflets and summaries of product characteristics. Eur J Clin Pharmacol 2021;77(2):251–60.
18. Sansom LN, ed. Australian pharmaceutical formulary and handbook. 26th edn. Canberra:Pharmaceutical Society of Australia;2024.
19. NPS MedicineWise. Consumer medicine information (CMI) explained. 2018. At: www.nps.org.au
20. Healthdirect. How to read Consumer Medicine Information (CMI). 2022. At: www.healthdirect.gov.au
21. Specialist Pharmacy Service. Advising on missed or delayed doses of medicines. 2023. At: www.sps.nhs.uk/articles/advising-on-missed-or-delayed-doses-of-medicines/
22. Actonel Once-a-month tablets. Consumer Medicines Information. eMIMS Plus Cloud [2024] At: www.emims.com.au/drug/search

Our authors

Dr Amy Page (she/her) PhD, MClinPharm, GradDipBiostat, GCertHProfEd, GAICD, GStat, FSHPA, FPS is a consultant pharmacist, biostatistician, and a senior lecturer at the University of Western Australia.

Hui Wen Quek (she/her) BPharm(Hons), GradCertAppPharmPrac is a pharmacist and PhD candidate at the University of Western Australia.

Our reviewer

Julie Briggs (she/her) BPharm, MPS, AcSHP

Conflicts of interest declaration

Hui Wen Quek is supported by an Australian Government Research Training Program (RTP) scholarship at the University of Western Australia.