Management of Opioids

One of the roles of the Accountable Officer (AO) for Controlled Drugs is to assure that good governance of controlled drugs (including and up to schedule 5) should apply in all health and social care settings and individual practices. If you have any concerns regarding the use of CD's, you should contact your AO for advice:

Refer to the various formulary treatment guidelines for use of opioids when treating certain conditions (see here).

For the treatment of pain in palliative care (see here).

See section 4.7.2 Opioid analgesics for list of formulary opioids.

Opioids Aware (Faculty of Pain Medicine), is a resource for patients and healthcare professionals to support prescribing of opioid medicines for pain.

Strong opioids should always be used as part of a multimodal strategy for pain management utilising NSAIDs and/or non-opioid painkillers, and/or non-pharmacological interventions when appropriate. It is important to review the risks and benefits of continued opioid therapy on a regular basis.

Opioids are not indicated for the 3 most common pain conditions:

The reason for starting an opioid for non-malignant pain needs to be clear. Set outcome goals before starting and consider the use of an opioid contract (see below).

When prescribing opioids, assess the patient's mental health and current or previous history of addiction to drugs or alcohol:

  • Mental health comorbidities and a history of significant emotional trauma are not a contraindication to opioid therapy but are a risk factor for opioid therapy becoming prolonged and for high doses to be used, and are a risk factor for addiction to prescribed opioids
  • Patients with a current or past history of addiction will need careful management and support in collaboration with specialists with expertise in substance misuse. See Management of pain in substance misuse disorders for further guidance.

Opioid analgesics are used to relieve moderate to severe pain. Repeated administration may cause dependence, tolerance or opioid induced hyperalgesia (see opioid side effects below), but this should not be a deterrent in the control of pain due to terminal illness. Dosages can escalate over time without a noticeable effect on the patient's pain or psychological distress. Recent research shows mood state and distress can modulate opioid efficacy. Evidence of early prescription requests or rapidly escalating dose should trigger a concern.

Strong opioids have ceiling effects for analgesia and side effects. Complete pain relief is not always achieved even with strong opioids at high doses in some pain conditions; this should be explained to all patients.

Do not prescribe more than one type of opioid at a time unless following specialist advice (e.g. co-prescription of oral morphine sulphate modified release and transdermal fentanyl). Injectable opioids should never be used as part of a strategy for chronic pain management, except in palliative care.

Opioids should be prescribed mainly as controlled release formulations with limited breakthrough only (e.g. 4 times daily when required). Avoid using large doses of breakthrough medication only. Morphine sulphate oral solution 10mg/5ml should never be prescribed 'when required' without a prescribed dose and dose interval. Morphine sulphate oral solution may contain alcohol, which may be harmful in certain patient groups. Refer to individual Summary of Product Characteristics

It is helpful to consider strong opioid prescribing in different dosage 'bands'. Although the dose which would constitute such bands in practice varies between individuals in terms of age and co-morbidity the dosage bands given below are included as a pragmatic clinical guide.

  • Low dose up to 50mg morphine equivalents orally in 24 hours. Withdrawal symptoms are unlikely on discontinuation. Rotation to a different opioid usually uncomplicated. Side effects become more prominent above 50mg morphine equivalent.
  • Intermediate dose 50 to 120mg morphine equivalents orally in 24 hours. Withdrawal symptoms may occur with discontinuation. Rotation to a different opioid may therefore require cross over prescribing over a period of time. Side effects likely.
  • High dose over 120mg morphine equivalents orally in 24 hours. Withdrawal symptoms likely with discontinuation: Seek advice from the Pain Management Clinic if considering rotation to a different opioid. Side effects likely, including opioid induced hyperalgesia.

MHRA Drug Safety Update (September 2020): Opioids: risk of dependence and addiction
Before prescribing opioids, discuss with the patient the risks and features of tolerance, dependence, and addiction, and agree together a treatment strategy and plan for end of treatment.

Advice for healthcare professionals:

  • Opioid medicines (opioids) provide relief from serious short-term pain; however longterm use in non-cancer pain (longer than 3 months) carries an increased risk of dependence and addiction
  • Discuss with patients that prolonged use of opioids may lead to drug dependence and addiction, even at therapeutic doses
  • Before starting treatment with opioids, agree with the patient a treatment strategy and plan for end of treatment (see subsection Opioid contracts below)
  • Explain the risks of tolerance and potentially fatal unintentional overdose, and counsel patients and caregivers on signs and symptoms of opioid overdose to be aware of (see opioids safety information leaflet - also available as a pdf leaflet)
  • Provide regular monitoring and support especially to individuals at increased risk, such as those with current or past history of substance use disorder (including alcohol misuse) or mental health disorder. See the advice above on assessing the patient’s mental health and current or previous history of addiction to drugs or alcohol when prescribing opioids. For patients with a current or past history of addiction, see Management of pain in substance misuse disorders for further guidance
  • At the end of treatment, taper dosage slowly to reduce the risk of withdrawal effects associated with sudden cessation of opioids; tapering from a high dose may take weeks or months (see subsection Tapering and stopping opioids below for practical advice)
  • Consider the possibility of hyperalgesia if a patient on long-term opioid therapy presents with increased sensitivity to pain (see subsection Opioid side effects for action to be taken in the event of opioid-induced hyperalgesia)
  • Consult the latest advice and warnings for opioids during pregnancy in the SPC and in clinical resources

Rotating/switching opioids

The guidance below is based upon the Opioids Aware resource and the following article: 'Equianalgesic doses of opioids – their use in clinical practice' written by local specialist Douglas Natusch (Br J Pain. 2012 Feb; 6(1): 43–46). Please also refer to the BNF and Summary of Product Characteristics for further information.

Opioid rotation or switching may be considered if a patient obtains pain relief with one opioid but is suffering severe adverse effects; or it may be required in the context of co-morbidity e.g. renal impairment. Following the guidance of local specialists it may be considered that a patient has developed tolerance over time to the analgesic effect of an opioid that was initially helpful, and the clinician may advise opioid rotation rather than dose escalation.

Consider the following points when rotating/switching opioids:

  • Switching from one opioid to another should only be recommended by a healthcare professional with adequate competence and sufficient experience in the management of pain and prescription of opioids.
  • If in any doubt over an opioid switch for a patient receiving palliative care, seek advice from the specialist palliative care team
  • It is recommended that conversion calculations are double checked with a colleague.
  • It is important to taper or stop opioid prescription if the medication is not providing meaningful pain relief (see formulary guidance below). The dose above which harms outweigh benefits is 120mg oral morphine equivalent/24hours. Increasing opioid load above this dose is unlikely to yield further benefits but exposes the patient to increased harm.
  • An individualised approach to switching opioids is necessary.
  • There is no definitive guide to equivalences. There is significant inter-individual variation in opioid pharmacokinetics and other variables such as nutritional status and concurrent medication. Equianalgesic tables and diagrams are often constructed using information from studies of different quality and the data quoted may have been derived from a different clinical context. Data needs to be treated as 'loose guidance' to avoid significant under- or overdosing.
  • Any dose regimen has to be taken in context of the patient's age, weight, co-morbid medical and mental state, as well as concurrent medication (both prescribed and over the counter).
  • The timescale over which the change is to be made needs to be planned – is there to be a period of crossover prescribing with a tapered reduction of the initial opioid?
  • The half-life and time to onset of action of the two drugs needs to be considered.
  • Patients who have been using opioids in the medium term or longer may have undergone physiological adaptations to chronic use. This may impact not only on subsequent analgesic requirements but also on withdrawal symptoms.
  • It is recommended not to target the equianalgesic dose but to take such a dose and make a 30–50% reduction as an initial target. In cases where dose ranges, rather than equianalgesic doses, are quoted it may be prudent to consider a dose reduction from the lowest point of the dose range. A dosage reduction may not be appropriate if the original opioid taken at the prescribed dosage failed to control the pain.
  • A dose reduction of at least 50% is recommended when switching at high doses (e.g. oral morphine or equivalent doses of 500mg/24 hours or more), in elderly or frail patients, or because of intolerable undesirable effects.
  • Ensure 4-hourly doses of short-acting immediate-release opioids are prescribed for breakthrough pain "when required".
  • The general advice is to calculate doses using morphine as standard (particularly important if the patient is prescribed multiple opioids) and to adjust them to suit the patient and the situation. The current dosage per 24 hours should be totalled including both regular and additional "when required" doses.
  • Switching between very high-dose opioids or switching to/from methadone is recommended for inpatients only with access to breakthrough medication and a fall-back plan. Specialist input is required.
  • Once the conversion has occurred, the dose of new opioid should be titrated carefully according to individual response and the patient monitored closely for the first 7-14 days for side effects and efficacy, especially when switching at high doses.
  • Conversion at high doses may lead to withdrawal symptoms from discontinuing the primary opioid. Replacing with another opioid even at what may be considered to be a similar potency does not prevent withdrawal from happening; a crossover period may be required for a few weeks.
  • Withdrawal symptoms (e.g. sweating, yawning and abdominal cramps, restlessness, anxiety) may occur if an opioid is stopped/dose reduced abruptly.

A guide to equivalent doses of opioid drugs, hosted on the Rowcroft Hospice website and often used in palliative care, has been developed by local specialists across the region. Please note this is not a definitive set of equivalences. Drug conversions can be challenging, it is recommended that conversion calculations are double checked with a colleague. If in any doubt over an opioid switch for a patient receiving palliative care, seek advice from the specialist palliative care team.

See section 4.7.2 Opioid analgesics for a full list of preparations.

Opioid side effects

Side effects are relatively common – these need to be considered and balanced with potential benefits. If patients continue to take medicines that provide limited analgesic benefit then they are exposed to harms unbalanced by the benefit that the medicines provide.

Tolerance to other opioid side effects such as constipation and nausea occurs at different rates to analgesic tolerance (see Pharmacological treatment of chronic non-malignant pain, Step 4 for guidance on how to manage suspected tolerance). The most common side effects include nausea, vomiting, constipation and drowsiness. Larger doses can produce respiratory depression and hypotension. Anti-emetic therapy should be considered with the initial titration of opioids (see section 4.6 drugs used in nausea and vomiting). When treatment with opioids exceeds 3 days, an osmotic laxative (or docusate which also softens stools) and a stimulant laxative e.g. senna, should be considered (see management of constipation in adults and section 1.6 laxatives).

Prescribers need to be aware of additional side effects that can occur with high dose opioid use (particularly above 120mg), when used long term:

  • Patients on high dose opioids have been shown to have a worse quality of life than those on a low dose and the same pain score
  • Hormonal changes - suppression of the hypothalamic-pituitary-gonadal axis (testosterone depletion reported in patients on long term methadone)
  • Immunological changes - potential, but poorly understood phenomenon
  • Opioid induced hyperalgesia (OIH) - A condition clinically suspected in patients on long term opioid analgesia whereby an increased sensitivity to painful stimuli is demonstrated. Although OIH can occur at lower doses it is more likely at higher doses. There are circumstances, for example in headache medicine, where much lower doses of even simple opioid analgesics cause pain and there is a concern there is no simple cut-off for this phenomenon. If suspected, opioids should be stopped. Patients on a very high dose of opioids may benefit from cautious dose reduction.
  • Osteoporosis
  • Problem drug use

Interaction with Monoamine Oxidase Inhibitors

The use of most monoamine oxidase inhibitors (MAOIs) with opioids is contraindicated or cautioned by manufacturers. There is conflicting information in the literature about the degree of risk of an interaction. Some opioid analgesics are associated with a risk of serotonin syndrome in combination with MAOIs; other combinations may result in opioid toxicity. When assessing the risk of combining an opioid with an MAOI, it is important to consider any other serotonergic drugs the patient is taking. It is recommended that the individual Summary of Product Characteristics (SPC) is reviewed before prescribing concomitant opioid and MAOI.

Opioids and driving

Patients prescribed opioids need to be aware of the risks of drowsiness and the effect on their ability to drive. Patients should not drive if they have changed their dose or if they feel unsafe: it is their responsibility to ensure they are fit to drive; further advice is available from the DVLA.

Tapering and stopping opioids

Opioids Aware (Faculty of Pain Medicine) states it is important to taper or stop the opioid regimen if:

  • The medication is not providing meaningful pain relief. The dose above which harms outweigh benefits is 120mg oral morphine equivalent/24hours. Increasing opioid load above this dose is unlikely to yield further benefits but exposes the patient to increased harm
  • The underlying painful condition resolves
  • The patient receives a definitive pain relieving intervention (e.g. joint replacement)
  • The patient develops intolerable side effects
  • There is strong evidence that the patient is diverting his/her medications

The Royal College of General Practitioners has produced factsheets regarding prescription and over-the-counter medicines misuse and dependence and include guidance to distinguish inadequate symptom control from drug misuse. The factsheets can be accessed here.

The decision to taper/stop an established opioid regimen needs to be discussed carefully with the patient and may require close collaboration between the patient, their carers and all members of the patient's health care team. Consideration should be given to physical and mental health co-morbidities including significant emotional trauma.

Discussions with the patient should include:

  • explanation of the rationale for stopping opioids including the potential benefits of opioid reduction (avoidance of long term harms and improvement in ability to engage in self management strategies)
  • agreeing outcomes of opioid tapering
  • arrangements for monitoring and support during opioid taper
  • symptoms and signs of opioid withdrawal
  • documented agreement of tapering schedule

Patients who are failing to derive benefit from large doses of opioids may need support from specialist services in order to reduce medication. Opioid tapering/cessation when patients are taking large doses is more likely to succeed if patients' emotional and mental health (including addiction) needs are identified and an appropriate plan for support established.

Practical advice for tapering and stopping opioids (individualise for each patient)
  • The dose of drug can be tapered by 10% weekly or two weekly
  • Some patients who have taken opioids for a long time might find even slower tapers (e.g. 10% per month) easier
  • Adjust the rate and duration of the taper according to the patient's response
  • The cardinal symptom of opioid withdrawal is pain. A pain flare-up may represent over rapid opioid tapering not a failure of analgesia. If the patient experiences a pain flare-up it may be necessary to pause the taper for 4-6 weeks to allow the flare to settle before continuing the reduction
  • Let patients know that most people have improved function without worse pain after tapering opioids. Some patients even have improved pain after a taper, even though pain might briefly get worse at first
  • Once the smallest available dose is reached, the interval between doses can be extended and opioids may be stopped when taken less than once a day.
  • Discuss the increased risk for overdose if patients quickly return to a previously prescribed higher dose
  • When withdrawing patients from tramadol, the reduction in serotonin levels must be considered alongside the withdrawal from the opioid
  • If a patient is on multiple opioids, there is no rule as to which opioid is stopped first, or if they are all gradually reduced at the same time. It is recommended that some immediate release opioid is provided for breakthrough, but its use should be strictly monitored.

Repeat prescriptions for opioids

In general, opioids should not be added to the repeat prescribing system but should be generated as acute prescriptions.

If an opioid has a demonstrable positive benefit for an individual patient and there is a robust system for monitoring use then consideration may be given for short-term authorisation of repeat prescriptions.

The prescriber and patient together should review the continuing benefit of opioid therapy and potential harms at regular intervals (at least twice each year).

Opioid contracts

An opioid contract is strongly recommended.

The goals of therapy should be agreed before starting opioid treatment and assessed at each review. These goals should be clearly documented. A formal opioid 'contract' can provide a useful basis for further discussion if medication use becomes poorly controlled or the agreed outcomes of therapy are not achieved. It is helpful to plan for the management of flare-ups in symptoms by means other than an increase in stable opioid dose.

Examples of local opioid contracts can be found via the following links:


Supplies of naloxone injection 400 micrograms in 1ml are required in the same clinical storage locations where diamorphine and morphine injections are stored, including in GPs' bags and bags held by out-of-hours providers (NPSA Safer Practice Notice 12; May 2006).


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