Missed Medication Doses

A missed or delayed dose of time critical medicines can cause harm to the patient or compromise the therapeutic effect, resulting in suboptimal therapy.

Knowledge of the half-life of a medication helps in identifying whether missed doses have any significant consequences. It aids in making recommendations on what to do when a dose is missed. The general rule of thumb for a medicine to be eliminated from the body is four to five half-lives. At this time the plasma concentration of the given medicine is generally below a clinically relevant concentration. While an occasional missed dose of most medicines has little consequence on therapeutic outcomes, delays or omissions for some medicines can lead to serious outcomes.

Missing a dose of medicines with a short half-life and/or rapid onset of action in relation to the dosing interval may lead to periods of sub-therapeutic plasma drug concentrations, leading to insufficient pharmacological activity.

Medicines with a long half-life stay in the body for longer. Thus, missing a dose may not cause a significant drop in drug levels, thereby reducing the risk of sub-therapeutic levels.

It is important to note that the clinical effects of some medicines are not directly related to their half-lives e.g. drugs 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.

The following medicines need strict adherence to dosing schedules to avoid potentially significant or even catastrophic long-term patient impact:

• Anticoagulants due to possible risk of thrombosis (e.g. enoxaparin missed dose could lead to deep vein thrombosis or pulmonary embolism which could be life threatening).
• Anticonvulsants due to risk of seizure activity, especially if omitted perioperatively.
• Antimicrobials due to risk of drug resistance, prolonged infection, incorrect interpretation of therapeutic drug monitoring.
• Bronchodilators due to risk of breathing issues.
• Immunosuppressants due to the risk of rejection or loss of disease control, depending on the indication.
• Oral contraceptives due to risk of contraceptive failure.
• Psychotropics due to risk of poor symptom control.
• Antidepressants as withdrawal symptoms may occur within hours of the first missed dose, particularly for agents with short half-lives (e.g. paroxetine or venlafaxine).
• Levodopa as a short delay in administration of levodopa-containing products for the treatment of Parkinson’s disease can worsen symptoms and cause rigidity, pain, tremor, increased risk of falls, as well as stress, anxiety and difficulty in communicating.

When specific information regarding a missed dose is not available, the general advice is to take the missed dose as soon as it is remembered if the dose is less than two hours late. If the dose is more than two hours late:

• 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 and wait until the next dose is due, and then continue taking the medicine at the usual times.

Unless specifically advised, it’s generally recommended not to take a double dose to make up for a forgotten dose.

The first place a patient should be instructed to look for advice regarding missed dose of their medication at their usual time is the Consumer Medicine Information (CMI).

Other ways patients can obtain information about missed doses are:

• Speaking to their pharmacist
• Contacting the relevant pharmaceutical company (details can usually be found on the company’s Australian website).
• Searching for CMI in Healthdirect’s medicines section at www.healthdirect.gov.au/medicines.