Regular benzodiazepine regimens for patients with ongoing agitation and restlessness in the last days of life

If a benzodiazepine is indicated, for patients who do not already take a regular benzodiazepine, in addition to an as-required benzodiazepine, consider starting regular therapy with the same benzodiazepine if agitation or restlessness is ongoing or if more than 3 as-required doses are needed in 24 hours.

Note: If using a regular benzodiazepine for agitation or restlessness in the last days of life, also prescribe an as-required benzodiazepine.

For patients who have been taking an as-required benzodiazepine for at least 24 hours, calculate the total amount taken in the previous 24 hours and give between half and the full total dose as a daily subcutaneous infusion—seek specialist advice if required.

For patients who have not been taking an as-required benzodiazepine for at least 24 hours, a suitable starting dose for regular benzodiazepine therapy by continuous subcutaneous infusion for agitation or restlessness in the last days of life is:

1clonazepam 0.5 to 2 mg/24 hours by continuous subcutaneous infusion12. Monitor response and adjust dose as needed. If response to treatment is inadequate or more than 3 as-required doses are needed in 24 hours, review therapy. If more than 4 mg in total is required in 24 hours, or if symptom relief is inadequate, seek specialist advice clonazepam

OR

1midazolam 5 to 20 mg/24 hours by continuous subcutaneous infusion1. Monitor response and adjust dose as needed. If response to treatment is inadequate or more than 3 as-required doses are needed in 24 hours, review therapy. If more than 60 mg in total is required in 24 hours, or if symptom relief is inadequate, seek specialist advice. midazolam

If a continuous subcutaneous infusion of benzodiazepine is not possible, use:

1clonazepam 0.2 to 1 mg sublingually, 12-hourly3. Monitor response and adjust dose as needed. If response to treatment is inadequate or more than 3 as-required doses are needed in 24 hours, review therapy. If more than 4 mg in total is required in 24 hours, or if symptom relief is inadequate, seek specialist advice clonazepam

OR

1clonazepam 0.2 to 1 mg subcutaneously, 12-hourly. Monitor response and adjust dose as needed. If response to treatment is inadequate or more than 3 as-required doses are needed in 24 hours, review therapy. If more than 4 mg in total is required in 24 hours, or if symptom relief is inadequate, seek specialist advice. clonazepam

For patients whose agitation and restlessness has not improved with a benzodiazepine, consider adding an antipsychotic—see Approach to drug therapy for agitation and restlessness in the last days of life.

For patients who already take a benzodiazepine, see Benzodiazepine therapy for agitation and restlessness in the last days of life in patients who already take a benzodiazepine.

For general information, see Principles of managing agitation and restlessness in the last days of life.

1 When starting or increasing the dose of a drug administered by a continuous subcutaneous infusion, it may take a few hours for the drug to reach a therapeutic concentration. Consider giving an as-required dose of benzodiazepine concurrently if timely control is needed.Return
2 Clonazepam may be adsorbed onto PVC infusion tubing; non-PVC tubing is recommended, or adjust the dose to effect.Return
3 Two to ten drops of clonazepam 2.5 mg/mL oral liquid is equivalent to clonazepam 0.2 to 1 mg. Do not count drops directly into the mouth; count drops into a spoon first.Return