Download Ketamine - Medicines Management

Doncaster & Bassetlaw Area Prescribing Committee Approved March 2016 V2.0
Guidance for the Prescribing of Ketamine injection or oral solution (Amber-G)
1.0 Introduction
This document sets out the guidance for the assessment and treatment of complex
severe pain and pain not fully responsive to opioids by ketamine, prescribed by
Consultants in Palliative medicine with GPs if shared care is agreed, when care is
initiated in secondary care and transferred to primary care for continuation.
This document should provide clear guidance to the GP and hospital prescriber,
regarding procedures to be adopted when clinical (and therefore treatment and
financial) responsibility for a patient on “ketamine” is shared between primary and
secondary care.
The decision to start a patient on “ketamine” with “complex severe pain or opioid side
effects” should be taken by a Consultant in Palliative Medicine with prescribing
transferred to GPs only when the patient is on a stable regime.
Recommendation is amber with guidance
2.0 Background Information
Ketamine is a short acting anaesthetic with analgesic properties at low doses. It is
used particularly for neuropathic pain, ischaemic limb pain and refractory cancer pain
and as an adjunct to opioid therapy. Ketamine may be given orally or by continuous
subcutaneous infusion via syringe driver either as a sole agent or in combination with
other agents. Ketamine is unlicensed for these indications and should only be
initiated by a Consultant in palliative medicine.
Indications
Pain unresponsive to standard therapies (postoperative, neuropathic, inflammatory,
ischaemic limb, myofascial and procedure-related).
3.0 Prescribing Information
Pharmacology
Ketamine has a variety of pharmacological actions, including interaction with Nmethyl-D-aspartate (NMDA) receptors, opioid receptors, muscarinic receptors and Na
ion channels. The analgesic effect of ketamine that is seen at sub-anaethetic doses
This document will be reviewed in the light of new or emerging evidence or by April 2021
Doncaster & Bassetlaw Area Prescribing Committee Approved March 2016 V2.0
is due to non-competitive antagonism of the NMDA receptor. Ketamine interacts with
specific binding site on the NMDA receptor, blocking the influx of Na and Ca. Binding
of ketamine will only occur when the ion channel has been opened though neuronal
excitation. The analgesic activity is believed to be due to attenuation of the ‘wind-up’
phenomenon by reducing the excitability of the neurons (2).
Ketamine is a schedule 2 controlled drug
As such it is exempt from controlled drug prescription requirements and is not subject
to safe custody requirements. However Accountable Officer arrangements mean that
it’s prescribing is monitored.
Adult dosage and administration:
Dose recommendation varies depending on oral or subcutaneous use and clinical
response.
Oral Ketamine:
Doses start at 10-25mg three to four times daily. The dose and frequency can
normally be increased in steps of 10-25mg up to a dose of 50mg four times daily
(higher doses may be used by consultants).
Subcutaneous Ketamine:
Start with 25-50mg over 24hours using a syringe driver and increase by 50mg
increments every 24hours until benefit is achieved. These shared care arrangements
apply for doses up to 200mg/day, higher doses will be under the care of the
consultant. It is unusual to require doses greater than 600mg per day.
When given via a syringe driver it can be irritant to the subcutaneous tissue. Dilute
with sodium chloride 0.9% to the largest possible volume.
The dose of any concurrently prescribed opioid may need to be reduced when the
ketamine is initiated.
Suitability in a Syringe Driver:
At usual shared care doses ketamine is compatible with alfentanil, diamorphine,
morphine, oxycodone, haloperidol, metoclopramide, levomepromazine, midazolam in
a syringe driver.
Ketamine is incompatible with cyclizine.
Ketamine is generally incompatible with dexamethasone but doses of (0.5-1mg)
dexamethasone or less may be added to syringe driver to prevent site irritation.
If more than two drugs are to be mixed in the same syringe, please refer to the
current Palliative Care Formulary or www.palliativedrugs.com or seek further
specialist advice from the consultants in palliative medicine.
This document will be reviewed in the light of new or emerging evidence or by April 2021
Doncaster & Bassetlaw Area Prescribing Committee Approved March 2016 V2.0
Preparations available:
Subcutaneous Ketamine:
Prescribe only 50mg/ml, 10ml vials – rational for choice .
Nursing staff who will be administering the sc or syringe driver ketamine must
have a clear understanding that a 10ml vial of 50mg/ml is being used. This is
based on best practice agreed with Doncaster Barnsley and Rotherham
Palliative care services following previous instances of drug administration
errors in those areas.
Supply via community pharmacy may take up to three working days after a
prescription has been issued, so planning for care at home at the end of life
needs to be as well coordinated as possible.
Oral Ketamine Solution
Prescribe only the 50mg/5ml oral solution
This is available as a pack size of 250ml and 500ml.
It is anticipated that a quantity of 500ml per month is adequate quantity for
most patients. This is an unlicensed “special” and will not routinely be stocked
by community pharmacy; hence a delay may occur with the initial supply and
repeated prescriptions.
.
Note this preparation has no preservative and expires 28 days from opening.
4.0 Consultant in Palliative Medicine Responsibilities








Assess patient’s pain with regard to appropriateness of ketamine use,
considering any contraindications.
Determine baseline BP, LFTs
Initiate and titrate the dosage regimen for ketamine, either as an inpatient in
the hospital or hospice, or on an outpatient/home visit assessment.
Assess response and side effects.
Arrange shared care with GP when patient is managed on a stable regimen.
Retain prescribing responsibility for patients on ketamine doses > 200mg/mg
Provide clear instructions, with a copy of this prescribing advice, in a letter to
the GP, community specialist palliative care nurses and the local hospitals.
The patient will have a copy of this letter and advice.
Provide a copy of this information to Out of Hours services in case of
deterioration or if the patient requires additional medications. The consultant
on call for palliative medicine can be contacted through Doncaster Royal
Infirmary switchboard for these patients and advice on symptoms and issuing
scripts out of hours.
This document will be reviewed in the light of new or emerging evidence or by April 2021
Doncaster & Bassetlaw Area Prescribing Committee Approved March 2016 V2.0








Provide patient/carer with relevant written information on use, side effects and
need for monitoring of medication.
Ensure the prescription written for the patient is for a 28 day supply for the oral
preparation, or an appropriate quantity of vials for subcutaneous use to ensure
continuity of supply in the community.
Strength of vial must be 50mg/ml, 10ml vial.
Strength of oral solution must be 50mg/5ml.
Review the patient’s response and continuing appropriateness of ketamine at
specified intervals, sending a written summary to the GP. This may be
facilitated by community specialist palliative care team.
Provide any other advice or information for the GP and district nursing,
hospital teams or hospice teams if required.
Provide clear advice for the pre-emptive prescribing of ketamine and any
syringe driver use.
Stop the treatment when no longer considered to be appropriate.
5.0 GP Responsibilities





Once stable, prescribe ketamine and arrange ongoing monitoring as advised
by and agreed with the specialist to a maximum dose of 200mg/day. Using
o Strength of vial must be 50mg/ml, 10ml vial (max 2 week duration).
o Strength of oral solution must be 50mg/5ml in 250 or 500ml units
Refer to specialist when symptoms fail to respond to the management of
analgesia or when a change of administration route may be indicated.
Review the patient at regular agreed intervals to monitor control of symptoms.
Identify adverse drug reactions and report to Specialist and CSM.
Liaise with community and specialist nurses regarding ongoing patient care.
6.0 District nursing team/community specialist palliative care nurses/ward
nursing teams/hospital specialist palliative care nurses responsibilities
 Should ensure that they have this advice and an understanding of the
formulations and route (oral and subcutaneous route) of the Ketamine
medication when admitting the patient/completing a care plan or first
assessment and reviews.
 Understand that the subcutaneous route will have vials of 50mg/ml 10ml vials
prescribed.
 Understand the time that it may take to obtain different formulations in the
community and work with the team and the patient to plan that the medication
does not run out.
 Be aware of the potential side effects and beneficial effects of ketamine from
this advice.
 Have the contact details for the GP and consultants in palliative medicine in
the patient’s care plan and understand who to contact if problems.
 Follow the usual policies for syringe drivers, ’Instruction to Administer’ and
care plans as for any syringe driver or subcutaneous medications prescribed
as per policy within the organization in which the nursing staff are employed.
This document will be reviewed in the light of new or emerging evidence or by April 2021
Doncaster & Bassetlaw Area Prescribing Committee Approved March 2016 V2.0
7.0 Adverse Effects, Precautions and Contraindications
Contraindications:
Intracranial hypertension and seizures are absolute contraindications.
Hypertension, cardiac failure, previous cardiovascular events and CVA are relative
contraindications.
Precautions:
Avoid grapefruit juice with oral ketamine.
Ketamine may cause drowsiness and dizziness and dizziness. Patients should be
advised not to drive (or operate machinery) if affected.
Concurrent doses of opioids may need to be reduced.
Dose adjustment may be necessary in the elderly and patients with liver impairment.
Adverse effects:
Vivid dreams, hallucinations, excessive salivation/secretions, and sedation are the
most commonly reported problems. Hypertension and tachycardia can also occur.
Occasionally, pain and inflammation can occur around the injection site.
Rarely the patient can develop psychotomimetic phenomenon involving euphoria,
dysphasia, blunted affect, psychomotor retardation and altered body image
(particularly with CSCI).
If the patient experiences dysphoria or hallucinations, contact the consultant. If
necessary midazolam or haloperidol should be prescribed as an interim measure e.g.
2.5-5mg midazolam subcutaneously or 1.5-5mg haloperidol orally or subcutaneously.
The Consultant in Palliative Medicine should then be contacted to agree dose
reductions and to arrange review
8.0 Common Drug Interactions
Plasma concentrations of ketamine may be increased by diazepam. Ketamine may
affect hepatic metabolism of warfarin, carbamazepine, phenytoin and theophylline.
This information is not inclusive of all prescribing information and potential
adverse effects. Please refer to the full prescribing data SPC, the BNF and the
current Palliative Care Formulary. Information is also available at
www.palliativedrugs.com
The Consultants in Palliative Medicine are available during working hours
through their secretaries and out of hours there is a consultant in Palliative
medicine available through DRI switchboard.
This document will be reviewed in the light of new or emerging evidence or by April 2021
Doncaster & Bassetlaw Area Prescribing Committee Approved March 2016 V2.0
10.0
Guidance Development
Reference
1. Palliative Care Formulary third edition (PCF3), R Twycross, A Wilcock;
palliativedrugs.com Ltd 2008. www.palliativedrugs.com
2. Drugs in Palliative Care, A Dickman; Oxford University Press 2010
Written By:
Dr L. McTague, Consultant in Palliative Care
Dr A. Carey, Consultant in Palliative Care
Dr M Fernando, Consultant in palliative Care
Reviewed by:
NHS Doncaster and Bassetlaw APC
Jan 2012
Reviewed by:
NHS Doncaster and Bassetlaw APC
March 2016
This document will be reviewed in the light of new or emerging evidence or by April 2021
KETAMINE for PAIN RELIEF
How does ketamine work?
How should I take ketamine?
Ketamine is given in divided doses throughout the day. It is started at a low
dose and increased gradually to find the right dose to control your pain. It is
generally prescribed as a 50mg/5ml liquid.
The table below will be completed by the doctor. Follow the instructions and
bring this information leaflet to your next appointment.
Ketamine Dose Regime:
Dose (in ml)
Number of Times
Daily
Number of Days
Ketamine works by slowing messages going to your brain.
Some of these
messages are telling the brain that it thinks a part of your body is hurt. By
slowing these messages down, the pain you are feeling will be reduced.
What is ketamine usually used for?
Ketamine is a general anaesthetic, a medicine which is used to put patients to sleep
before an operation. The doses used for pain relief are much smaller than those
used for anaesthetic use.
The drug is not licensed for use as a painkiller, but it is used by specialists for this
reason because research has shown that ketamine can be effective for relieving pain.
How long will I have to take ketamine for?
If ketamine is helpful in reducing your pain, you can stay on it and your treatment
will be regularly reviewed.
Do I need any tests whilst I’m taking ketamine?
Your doctor will check your blood pressure regularly. You will also need blood tests
to check on the liver if you need to take this long-term.
Are there any side effects?
All medicines have side effects, but they do not happen in everyone who takes them.
Why do I need ketamine?
Ketamine is used to treat types of pain that have not been relieved by conventional
painkillers. It can be used by itself or in combination with other painkillers to
improve your pain relief.
Ketamine can cause drowsiness, dizziness, hallucinations, feelings of detachment and
feelings of euphoria. It can sometimes cause disturbances in vision and hearing or
increased blood pressure.
Will I still be able to drink alcohol?
If ketamine makes you feel drowsy or dizzy, then drinking alcohol may increase these
side effects.
Because of this, we advise that you should avoid drinking alcohol if you are affected.
Will I still be able to drive?
Ketamine can cause drowsiness. If you feel affected by this, we advise that you
should not drive until the effects have worn off.
The information in this leaflet is not intended to replace your doctors advice. If you
require more information or have any questions, please speak to your doctor, nurse or
pharmacist, or contact one of the following:

Your MacMillan Nurse

Hospital MacMillan Nurses (01302 366666 ext 3142)

Pharmacy Medicines Information (01302 553201)

St Johns Hospice (01302 796666)
This leaflet was adopted with permission from a leaflet produced by ©Chesterfield
Royal Hospital NHS Foundation Trust
Is it safe for me to take other medicines?
The original leaflet is available via the following link:
Before you take or buy any new medicines (including herbal remedies) tell your
Doctor or Pharmacist that you are taking ketamine and ask their advice.
http://www.chesterfieldroyal.nhs.uk/patients/patientinfo/atoz/K
What should I do if I forget to take a dose?
You should take a missed dose as soon as you remember. However, if it is almost time
for your next dose, wait until then to take your medicine and skip the missed dose.
Do not try to ‘double up’ to make up for your missed dose.
Remember:
This medicine has been prescribed for you. It should not be taken by anyone who
has not had them prescribed by a doctor.
Keep all medicines out of the reach of children.
Additional information: