Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol

ABSTRACT

Introduction: A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life.

Areas covered: This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol).

Expert opinion: The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.

KEYWORDS:

• Haloperidol
• midazolam
• morphine
• palliative care
• pharmacokinetics
• terminal illness

Article highlights

• In terminally ill patients, pharmacokinetics may be altered as a result of co-morbidities and physiological changes that occur at the end stage of life.

• The absorption of orally administered drug, can be altered significantly as a results of GI symptoms. In the palliative phase GI problems should be closely monitored, and medication (both dose and route of administration) should be reassessed if changes in GI motility occur.

• The volume of distribution of drugs can vary in terminally ill patients due to changes in body composition and plasma proteins. This is particularly relevant for drugs for which rapid response is desired.

• Drug metabolism can be diminished in case of liver disease, dehydration, inflammation or cachexia. Care givers should be aware of different reaction in patients with these symptoms and should look out for signs of altered efficacy and side effects in these patients, especially in the case of drugs with active metabolites.

• Renal eliminated drugs (or metabolites) can accumulate in the final days of life if fluid intake is limited, which can cause side effects due to accumulation of drugs or metabolites

• As the interaction of drugs with the physiology of dying is complex pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.

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Acknowledgments

The authors would like to thank W Bramer (Medical Library, Erasmus Medical, Centre) for assistance with the literature search.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.