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Subcutaneous clonidine in palliative care

Palliative care
Red – For medicines normally initiated and used under specialist guidance

Introduction

The guide is intended for use in primary and secondary care to support the management of patients receiving clonidine injection for refractory pain or refractory agitation at the end of life, especially when trying to avoid sedation or the use of an antipsychotic.

Clonidine injection should only be started by a specialist in palliative medicine and patients require ongoing specialist supervision.

Description

Clonidine is an alpha-2 receptor agonist, used orally for hypertension, migraine prevention, vascular headaches and menopausal symptoms, particularly flushing and vasomotor conditions.

Preparations

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Note: Administration via the subcutaneous route is off-label use.

Clonidine injection 150 micrograms/mL injection 1mL Ampoules
NOTE: For continuous subcutaneous infusion (CSCI) use either water for injection or sodium chloride 0.9% as diluent.

Indications

In patients:

  • whose pain is poorly responsive to standard therapies or where other therapies are deemed inappropriate.
  • with refractory agitation at the end of life.

Contraindications

  • Severe bradycardia.

Refer to Summary of Product Characteristics (SPC) (clonidine hydrochloride) for a full list of contraindications.

Cautions

Use with caution in patients with cerebrovascular disease, heart failure, mild to moderate bradycardia or peripheral vascular disease.

Monitoring:

Take heart rate (HR) and blood pressure measurements:

  • at baseline before dosing
  • 1 hour and 4 hours after the first bolus dose and after CSCI dose increases, and
  • daily at other times.

There is little specific evidence to support the frequency of monitoring, but a pragmatic approach should be taken, particularly if clonidine is used at end of life, where the patient is bed bound, and monitoring will not be beneficial.

Patients should be counselled about the risk of sedation and the risk of hypotension (including postural), particularly if they are still mobile.

Drug interactions:

Medications with alpha-2 antagonistic properties, such as mirtazapine or antipsychotic medicines, may reduce, prevent or abolish the effects of clonidine.

Other medications which lower either BP or HR can have an additive effect.

Liver impairment: not significantly impacted.

Renal impairment: half-life is increased (doubled) in those with renal impairment, so a smaller dose may be appropriate.

Side effects

Constipation, depression, dizziness, dry mouth, fatigue, headache, nausea, postural hypotension, salivary gland pain, sedation, sexual dysfunction, sleep disorders, vomiting.

Delusions, hallucination, malaise, paraesthesia, Raynaud's phenomenon, skin reactions.

Dose and administration

Initial administration of clonidine for either of above indications:

  • Give an initial dose of 75 micrograms subcutaneously (SC) immediately.
  • If no benefit, repeat after 1–2 hours.
  • If still no benefit after two doses, consider alternative therapies.

If benefit after one bolus dose:

  • start clonidine 150 microgram/24 hours CSCI and 75 micrograms SC as required up to four times per day.

If benefit after two bolus doses:

  • start clonidine 300 microgram/24 hours CSCI and 75 micrograms SC as required up to four times per day.

If necessary, increase the CSCI by 150 micrograms every 1–2 days.

Note

  • Typically, the effective dose is 300–600 microgram/24 hours.
  • Maximum recommended dose is ≤1,500 microgram/24 hours.

Discontinuing clonidine: patients on long-term administration may experience rebound effects, hypertension or agitation if clonidine is suddenly stopped. If possible, titrate dose down over 3–7 days as appropriate.

Practice points

  • Checking blood pressure may be less important for patients with refractory agitation at the end of life as they are likely to be less mobile.
  • There are some reports of incompatibility of clonidine with other medications in a syringe pump.

References

Howard P, Curtin J. BMJ Supportive & Palliative Care 2022;0:1–5. doi:10.1136/bmjspcare-2022-003651

Charlesworth, S. (Ed.). (2020). Clonidine Palliative Care Formulary (7th ed.). Pharmaceutical Press. Accessed at MedicinesComplete