Therapeutic implications of drug "holidays'.

While a patient may appear to be fully compliant with respect to quantity of medication ingested, the timing of doses can vary considerably. This may introduce protracted intervals between doses, particularly if dosing frequency is greater than once daily. This commonly presents in the form of drug holidays, where dosing is omitted for 1 or more days, followed by a resumption of full-strength dosing, possibly resulting in excessive drug effects when dosing suddenly resumes, rebound effects when dosing is suddenly stopped and a period without effective drug action. Poor compliance has not only been associated with poorer treatment outcome, but also with financial consequences. It has been suggested that hospitalization due to non-compliance accounts for 11.7% of all healthcare expenditure in the U.S.A. Differences between drugs, in terms of both their concentration-time profiles and their duration of action, will lead to some agents being more effective than others in the face of interruptions in dosage. A drug with an intrinsically long duration of action, such as the calcium antagonist amlodipine, will provide better therapeutic coverage than those with a shorter duration of action and therefore minimize effects generated by an intermittent pattern of dosing.