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My Patient Missed a Dose; What Should I Advise?

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Prescriber Update 37(2): 28-29
June 2016

Healthcare professionals are often asked by patients for advice on missed doses.

When managing a missed dose, consider:

the patient’s condition and indication for which the medicine is being used
the pharmacokinetics of the medicine, in particular the half-life
the pharmacodynamics of the medicine.

The Patient's Condition and Medicine Indication

The severity of a patient's condition may determine whether clinically significant effects will occur due to a missed dose¹.

Vulnerable patients include those taking medicines with a low therapeutic index, or requiring a minimum effective concentration (eg, anticonvulsants and anticoagulants)¹. In contrast, for most patients with conditions such as hypertension or hypercholesterolaemia, a single missed dose will be of little consequence¹.

Pharmacokinetics

The half-life of a medicine is useful when deciding how to manage a missed dose. It takes four to five half-lives for a medicine to be completely eliminated¹. The half-life can usually be found in the medicine data sheet that can be accessed from the Medsafe website (www.medsafe.govt.nz/profs/datasheet/DSForm.as).

In general, medicines or their active metabolites with a long half-life create fewer problems when a dose is missed than medicines with a short half-life¹. Medicines with a short half-life may lose their therapeutic effect rapidly¹. For example, patients taking paroxetine (half-life of about one day²) may experience withdrawal symptoms if they miss or are late taking a dose. Whereas, patients taking fluoxetine may not experience withdrawal symptoms if they miss a dose as the active metabolite has a long half-life (four to 16 days)³.

However, missing several consecutive doses of a medicine with a long half-life can make it difficult to re-establish therapeutic concentrations¹. Loading doses may be needed in these situations for some medicines such as digoxin¹.

Pharmacodynamics

The clinical effect of some medicines is related more to their pharmacodynamic, rather than pharmacokinetic, properties. This usually occurs when the medicine is:¹

acting via an irreversible mechanism (eg, aspirin's effect on platelets)
acting via an indirect mechanism (eg, warfarin's effect on blood coagulation).

Medicines with first-dose effects (eg, ACE inhibitors) may need to be restarted at a lower dose than the patient’s maintenance dose to avoid adverse effects¹. Similarly, a dose reduction may be needed for medicines where tolerance occurs (eg, opioids) if more than one dose has been missed.

Overall, few studies have examined the clinical significance of a missed dose¹.

Provide Education

Talk to patients about using consumer medicine information (CMI). CMI are available for most commonly prescribed medicines and are produced by the medicine sponsor. CMI include a section 'If you forget to take it' (Table 1). CMI can be accessed from the Medsafe website (www.medsafe.govt.nz/Medicines/infoSearch.asp).

Make sure patients know which medicines they should not forget to take and who to consult if they miss a dose.

Table 1: What to do in the event of a missed dose (adapted from the CMI for each medicine; this is not an exhaustive list)^4-7

Medicine	Consumer Medicine Information
Dabigatran	A forgotten dose can be taken up to six hours prior to the next dose. The dose should be omitted if the remaining time is less than six hours to the next dose. A double dose should not be taken.
Alendronate (weekly)	The forgotten dose can be taken the next morning. Two tablets should not be taken on the same day. The patient should then return to taking one tablet once a week.
Phenytoin	A forgotten dose can be taken up to four hours prior to the next dose. If the patient remembers within four hours of the next dose they should skip the dose and take the next one as scheduled. A double dose should not be taken.
Carbamazepine	A forgotten dose can be taken up to two hours prior to the next dose. If the next dose is due within less than two hours the patient should skip the missed dose then take the next dose as normal. A double dose should not be taken.

References

Gilbert A, Roughead L, Sansom L. 2002. I’ve missed a dose; what should I do? Australian Prescriber 25(1): 16-18. URL: www.australianprescriber.com/magazine/25/1/16/8 (accessed 22 March 2016).
Mylan New Zealand Ltd. 2014. Loxamine Data Sheet 25 September 2014. URL: www.medsafe.govt.nz/profs/datasheet/l/loxaminetab.pdf (accessed 2 May 2016).
Actavis New Zealand Ltd. 2014. Arrow-Fluoxetine Data Sheet 20 August 2014. URL: www.medsafe.govt.nz/profs/datasheet/a/arrowfluoxetinetab.pdf (accessed 2 May 2016).
Boehringer Ingelheim New Zealand Ltd. 2015. Pradaxa Consumer Medicine Information June 2015. URL: www.medsafe.govt.nz/consumers/cmi/p/pradaxa.pdf (accessed 22 March 2016).
Merck Sharp & Dohme New Zealand Ltd. 2015. Fosamax Once Weekly Consumer Medicine Information August 2015. URL: www.medsafe.govt.nz/consumers/cmi/f/FosamaxWeekly.pdf (accessed 22 March 2016).
Pfizer New Zealand Ltd. 2015. Dilantin Consumer Medicine Information December 2015. URL: www.medsafe.govt.nz/consumers/cmi/d/DilantinOral.pdf (accessed 22 March 2016).
Novartis New Zealand Ltd. 2014. Tegretol Consumer Medicine Information October 2014. URL: www.medsafe.govt.nz/consumers/cmi/t/Tegretol.pdf (accessed 22 March 2016).