Treatment of pain using 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:

  • To report CD issues or concerns contact via email:
  • To raise concerns urgently please telephone 01392 314657 or 01726 627808

Supplies of naloxone 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)

Pethidine produces prompt but short-lasting analgesia; it is less constipating than morphine, but even in high doses is a less potent analgesic. It is not suitable for severe continuing pain. There is a danger of the accumulation of norpethidine with repeated dosing especially in patients who have renal impairment. For these reasons pethidine is not included in the formulary. Stat doses of NSAID suppositories may be useful in renal and biliary colic (see section 10.1 Drugs used in rheumatic diseases and gout)

For peri-operative analgesia (including fentanyl and alfentanil) see BNF Section 15.1.4

NPSA Rapid response July 2008: reducing dosing errors with opioid medicines

When opioid medicines are prescribed, dispensed or administered, in anything other than acute emergencies, the healthcare practitioner concerned, or their clinical supervisor, should:

  • Confirm any recent opioid dose, formulation, frequency of administration and any other analgesic medicines prescribed for the patient. This may be done for example through discussion with the patient or their representative (exercise care in accepting self-report from patients with dependence or suspected drug dependence), the prescriber or through medication records
  • Ensure where a dose increase is intended, that the calculated dose is safe for the patient (e.g. for oral morphine or oxycodone in adult patients, not normally more than 50% higher than the previous dose)

Approximate equivalent dosages of opioids

Oral morphine Oral oxycodone BuTrans® Buprenorphine patches Non-Formulary Transtec® Buprenorphine patches Matrifen® Fentanyl patches
12mg 24-Hour total dose 5 micrograms / hour
15mg 24-Hour total dose
20mg 24-Hour total dose 10 micrograms / hour
30mg 24-Hour total dose 15mg 24-Hour total dose
40mg 24-Hour total dose 20mg 24-Hour total dose 20 micrograms / hour
45mg 24-Hour total dose 22mg 24-Hour total dose 12 micrograms / hour
60mg 24-Hour total dose 30mg 24-Hour total dose 35 micrograms / hour
60mg 24-Hour total dose 30mg 24-Hour total dose 35 micrograms / hour
90mg 24-Hour total dose 45mg 24-Hour total dose 35 micrograms / hour 25 micrograms / hour
90mg 24-Hour total dose 45mg 24-Hour total dose 52.5 micrograms / hour 25 micrograms / hour
120mg 24-Hour total dose 60mg 24-Hour total dose 52.5 micrograms / hour 25 micrograms / hour
135mg 24-Hour total dose 52.5 or 70 micrograms / hour 25 micrograms / hour
145mg 24-Hour total dose 52.5 or 70 micrograms / hour
180mg 24-Hour total dose 90mg 24-Hour total dose 70 micrograms / hour 50 micrograms / hour
190mg 24-Hour total dose 70 micrograms / hour 50 micrograms / hour
224mg 24-Hour total dose 50 micrograms / hour
270mg 24-Hour total dose 135mg 24-Hour total dose
360mg 24-Hour total dose 180mg 24-Hour total dose 100 micrograms / hour


  • Medicines Q&As "What are the equivalent doses of oral morphine to other oral opioids when used as analgesics in adult palliative care?" 19th October 2009 UKMi
  • Opiate Conversion Doses (Gwent Guidance) October 2010
  • Summary of Product Characteristics for Transtec® patches
  • Summary of Product Characteristics for Matrifen® patches
  • British National Formulary No.63 (March 2012) p21.

Important Notes:

  1. The dosage equivalencies shown in the guide above are only approximate because comprehensive data are lacking and there is significant inter-individual variation. This variation is demonstrated, for example, with 100mg oral tramadol being quoted as approximately equivalent to between 10mg and 20mg of oral morphine
  2. These dosage equivalencies are based on data in palliative care medicine. No data could be found that would indicate different equivalencies for treating other patient groups
  3. When converting between opioids consider the total dosage per 24 hours being taken, including both regular and additional 'when required' doses. If the patient is on multiple opioids, it helps to convert them all to oral morphine equivalents
  4. When converting, particularly to a "stronger" opioid, consider an initial dose reduction of 25-50% from the calculated equianalgesic dosage (or choose a dosage at the lower end of the equivalent dosage range of the new opioid), and ensure that 4-hourly doses of PRN short-acting doses of opioid (e.g. Oramorph®) are prescribed for breakthrough pain
  5. However, a dosage reduction may not be appropriate if the original opioid taken at the prescribed dosage has failed to control the pain
  6. Once conversion has occurred, the dosage of the 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

Potency of codeine and tramadol in comparison to stronger opioids

Prescribers are reminded that the potency of the weaker opioids, codeine and tramadol, should not be underestimated. Regular doses of these drugs can equate to significant doses of morphine.

120mg of codeine over a 24 hour period approximates to between 15 and 30mg of morphine over the same period. 240mg approximates to a total daily dose of 45mg of morphine.

200mg of tramadol in a 24 hour period approximates to 30mg morphine over the same period, 400mg approximates to a total daily dose of 60mg of morphine.

(Please note: these equivalencies are only included as a cautionary guide, they are not to be used for dose conversion)

Use of strong opioids

There are specific circumstances when the use of strong opioids may be appropriate for the management of chronic non-malignant pain. It may be appropriate for a specialist to supervise treatment and the patient should be assessed at regular intervals.

Opioid analgesics are used to relieve moderate to severe pain. Repeated administration may cause dependence and tolerance (or opioid induced hyperalgesia), but this should not be a deterrent in the control of pain due to terminal illness.

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). 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.

Avoid concomitant use of opioid analgesics in patients taking monoamine oxidase inhibitors (MAOIs) and for 2 weeks after stopping MAOIs.

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. They should notify the DVLA that they are taking opioid medicines.

Strong opioids should always be used as part of a multimodal strategy for pain management.

  • Remember like all analgesics 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.
  • The reason for starting an opioid for non-malignant pain needs to be clear. Set outcome goals before starting in terms of physical function and sleep, not simply pain relief. Frequently review that these have been achieved.
  • Injectable opioids should never be used as part of a strategy for chronic pain management, except in palliative care.
  • Avoid using large doses of breakthrough medication only. Opioids should be prescribed mainly as controlled release formulations with limited breakthrough only (e.g. 4 times daily when required). Oramorph should never be prescribed when required without a prescribed dose and dose interval.
  • A history of previous alcohol / problem drug use is a 'red flag' for potential problems with prescribing (see below).
  • Evidence of early prescription requests or rapidly escalating dose should trigger a concern
  • 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
    • Intermediate dose 50 to 150mg 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
    • High dose 150mg plus 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
  • Patients taking strong opioids for pain relief will become tolerant/dependent on the opioid and often have pain. 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.

Prescribers need to be aware of additional (to those more commonly known) side effects that can occur with high dose opioid use, long term:

  • Patients on high dose opioids have been shown to have a worse quality of life than those on a low dose
  • 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 - A condition clinically suspected in patients on long term opioid analgesia whereby an increased sensitivity to painful stimuli is demonstrated. Patients on a very high dose of opioids may benefit from cautious dose reduction

Addiction History: It is recommended opioids in this context are prescribed within a specific framework: single medical prescriber and contract; regular monitoring of use (e.g. warning on practice computer system and to Out of Hours service if necessary) and emphasis on the use of controlled release opioid formulations only if necessary.

Seek early advice from a Pain Management Consultant or Addiction Medicine Consultant if conflicts develop over prescribing or before starting strong opioids if there are concerns.

Please refer to British Pain Society document 'Pain and substance misuse: improving the patient experience'

Please also refer to Management of pain in substance use disorders, see below

Prescribing transmucosal fentanyl preparations

Effentora® buccal tablets and Abstral® sublingual tablets are the formulary choice of transmucosal fentanyl.

These are licensed for the treatment of breakthrough pain in patients already receiving background opioid treatment for chronic cancer pain.

Do not prescribe for patients with acute pain, postoperative pain, headache/migraine or sports injuries.

Patients should be assessed by the palliative care or pain teams before commencement with transmucosal fentanyl to ensure full assessment of pain.

The effective control of chronic pain with around the clock opioids should be achieved prior to commencing treatment. Do not use in opioid non-tolerant patients – all patients must be on background opioid treatment.

The doses of Effentora® and Abstral® are not interchangeable.


  1. Assess pain control: Is persistent malignant pain controlled?
    1. Yes - but episodes of breakthrough pain not controlled – progress to 2
    2. No - Further titration of around the clock background opioids e.g. Zomorph®, oxycodone m/r, fentanyl patch
  2. Assess and diagnose breakthrough pain: Flare of severe pain, sudden onset and short duration, on a background of controlled pain. Pattern, cause, character, location - does it occur when there is activity or nursing interventions?
  3. Trial of Oramorph® or oxycodone: Prescribe a when required dose of Oramorph® or immediate release oxycodone (1/6 of the total 24hour background dose)
  4. Success with immediate release morphine or oxycodone: Continue with this, keeping under assessment for side effects and speed of onset.
  5. Unsuccessful with immediate release morphine or oxycodone - use transmucosal fentanyl. Onset of pain relief is too slow, persistent drowsy side effects due to long length of action, worsening constipation. Patient in pain due to lack of concordance with Oramorph® or oxycodone

Starting transmucosal fentanyl

Constant reassessment is needed for accurate symptom control.

There is no direct conversion from the other opioids and the correct dose must be established by titration. If patient has previously used another transmucosal fentanyl preparation the correct dose must be re-titrated.

Stop current transmucosal fentanyl and start replacement transmucosal fentanyl at next breakthrough pain episode.

Initiating Effentora:
  • Initiate treatment with Effentora® 100 micrograms. If successful pain control, prescribe this dose.
  • If pain is not controlled after 30 minutes, a second Effentora® tablet of the same strength should be given. Pain control must be assessed.
  • Patients should wait at least 4 hours before treating another breakthrough pain episode with transmucosal fentanyl.
  • If the episode required the use of the second tablet, an increase in dose to the next strength should be given at the next episode.
  • Continue this routine until the correct dose is found.
  • Doses above 800 micrograms were not evaluated in clinical studies.
  • Once titrated to an effective dose, patients should use only one tablet, of the correct dose, per breakthrough pain episode
Initiating Abstral:
  • Abstral® 100 micrograms. If successful pain control, prescribe this dose.
  • If pain is not controlled after 15-30 minutes, a second Abstral® tablet of the same strength should be given. Pain control must be assessed.
  • Patients should wait at least 2 hours before treating another breakthrough pain episode with transmucosal fentanyl.
  • If the episode required the use of the second tablet, an increase in dose to the next strength should be given at the next episode.
  • Continue this routine until the correct dose is found.
  • Doses above 800 micrograms were not evaluated in clinical studies.
  • Once titrated to an effective dose, patients should use only one lozenge, of the correct dose, per breakthrough pain episode

Dose re-adjustment

When patients require more than one dose for several consecutive episodes, having been previously stable:

  • If more than 4 episodes occur in 24 hours reassess the background opioid dose
  • If the patient feels very dizzy or very sleepy before the tablet or lozenge is completely dissolved, they should rinse their mouth with water and spit the remaining pieces of the tablet into a sink or toilet right away. The next dose should be reduced.
  • If pain control is not achieved at the maximum dose for the product (see above) an alternative treatment must be found

Prescription of transmucosal fentanyl preparations for breakthrough pain

All prescriptions must be written by brand as Effentora® or Abstral® and not as generic fentanyl. This will enable the correct formulation to be dispensed. The doses of Effentora® and Abstral® are not interchangeable.

All prescriptions should be reviewed after one week.

If breakthrough pain remains a regular issue and is requiring frequent treatment a review of the long acting, background opioid medication, should be done and the dose increased as needed.

Treatment of Non- Malignant Pain

Key points:
  • Ensure adequate trial of all drugs before moving on to next step
  • Ensure compliance is good e.g. paracetamol is being taken at proper dose – 1g six hourly, opioids are being taken at prescribed dose before dose increase
  • The oral route is to be preferred over all other routes. All analgesics are more effective when given regularly. Multimodal analgesia is more effective than a single agent alone
  • Pain greater than 3 months duration is defined as chronic
  • If analgesia fails, consider neuropathic pain
  • Effective analgesia results in at least 30% reduction in mean pain score
  • Usually opioids will not completely relieve chronic pain
  • Manage patient expectation
  • Caution using morphine and codeine where eGFR less than 30mL/min.
  • Use oxycodone instead of morphine for patients with renal impairment (eGFR less than 30mL/min)
  • Only prescribe an NSAID if the benefits of treatment clearly outweigh the risks and a need for an anti-inflammatory agent is identified. Avoid long term use if possible; refer to Prescribing non-steroidal anti-inflammatory drugs
  • If an NSAID is used for analgesia alone, it is recommended that the drug should be changed if no response is obtained after 1 week. If an anti-inflammatory action is required, then a trial of 3 weeks should be allowed
  • Multiple drugs should not be used when stepping up analgesia. Stop previous drug when starting new drug. Exceptions: Paracetamol plus NSAID can be used with opioid formulations for breakthrough pain
  • Consider non pharmacological treatments – physiotherapy or TENs. Pain is a bio-psychosocial phenomenon. In high levels of distress or psychopathology, analgesia alone is unlikely to prove effective

Strong opioid use in chronic non-malignant pain:

Please consult the British Pain Society for further information:

Risks of strong opioid use, particularly above 150mg morphine equivalent per day include immunosuppression, sex hormone suppression, osteoporosis and problem drug use. Tolerance to other opioid side effects such as constipation and nausea occurs at different rates to analgesic tolerance. Tolerance and dependence will universally occur.

Assess the patient's mental state before prescribing. Severe anxiety, depression or other psychiatric diagnoses make problem opioid use more likely.

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.

Patients who do not gain 30-50% pain relief from an agreed dose of opioid within 2-4 weeks should have that drug withdrawn. Titration of doses should occur gradually by 20-30% every week. Failure to demonstrate improved pain relief should trigger a re-evaluation.

Generally, use modified release opioids on a regular basis. There is not usually a basis for giving immediate release or breakthrough opioid analgesia. Oramorph is to be avoided in chronic non-malignant pain.

Step 1
  • Regular Paracetamol 1g six hourly (or appropriate lower dose)
  • Add in NSAID such as naproxen (maximum 500mg 12 hourly) or ibuprofen (maximum 800mg eight hourly) unless contraindicated. Consider gastro-protection; stop if not effective (see notes above).

Review regularly: Add in weak opioid as a combination drug if NSAID/paracetamol not sufficient

Step 2
  • Co-codamol 8/500 two tablets six hourly when required, or
  • Co-dydramol 10/500 two tablets six hourly when required, or
  • Co-codamol 30/500 two tablets six hourly when required

Review regularly: Prescribe one drug at a time in step 2 to achieve effective analgesia, stepping up as necessary

Stop and review before starting tramadol.

Set a maximum dose (tramadol 100mg six hourly = Zomorph 40mg daily), treatment period (e.g. one month) and acceptable response (e.g. 50% reduction in pain). Withdraw treatment gradually and monitor for low mood. Assess abuse potential.

Assess character of pain - if neuropathic follow guidance Neuropathic pain

Step 3
  • Switch co-codamol to paracetamol and start tramadol 50mg, increasing towards 100mg six hourly, immediate release preparations. There is an increased risk of CNS toxicity when serotonergic drugs (such as SSRIs) are taken with tramadol

Stop and review before starting strong opioid.

Consider written contract. Set maximum dose (e.g. Zomorph® 40mg 12 hourly), treatment period (e.g. one month) and acceptable response (e.g. 50% reduction in pain). Assess abuse potential.

Please refer to British Pain Society Guidelines: Opioids Aware

For patients: British Pain Society: Opioids Aware

Step 4
  • Zomorph® 10mg 12 hourly as starting dose. Remember Zomorph® capsules can be opened up for ease of swallowing.
  • Butec® patches: only in patients with cognitive deficit, or with swallowing difficulties and after a trial of soluble/liquid medication. Remember Zomorph® capsules can be opened up for ease of swallowing.

Review regularly:

  • Do not use fentanyl patches for non-cancer pain
  • Oxycodone and tapentadol are for specialist initiation only.
  • Avoid immediate release strong opioids in chronic pain.
  • Do not prescribe more than one opioid
Step 5 Pain Clinic Management
  • Failure to achieve adequate analgesia, concerns about excessive or uncontrolled opioid use (or rapid escalation) or reaching an agreed target dose should trigger referral to a pain management specialist (suggest 120-180mg morphine equivalent per 24 hours).
  • Problem drug use should trigger referral to an addiction specialist.

Management of pain in substance use disorders

The management of acute and chronic pain in patients with substance use disorders is a complex neurobiological phenomenon and presents the clinician with a number of challenges. In this brief guide we will aim to cover the main points and also refer the reader to more comprehensive resources including reference (1).

In summary:

  • A comprehensive assessment of both pain and substance misuse (including alcohol) is essential when managing pain in patients with current or past substance use disorders.
  • Although caution is necessary, patients who are dependent on opioids or have a history of drug dependence may be treated with opioid analgesics when there is a clinical need. Treatment with opioid analgesics in this patient group should normally be carried out with the advice of specialists.
  • Consider non-pharmacological interventions also in the development of a pain management plan.
  • The opioid maintenance dose of methadone or buprenorphine should usually remain at its maintenance dose except where there may be an issue with hyperalgesia or “blocking doses" of buprenorphine (12mg or above) which may interfere with the pain management plan (see below).
  • Consider splitting the dose of methadone and buprenorphine (every 6-8 hourly) within the pain management plan as this may provide a better pain management profile than once daily dosage in addition to the defined pain management plan.
  • Opioid induced hyperalgesia may result in an increase in pain sensitivities. This phenomenon is common in substance users who are maintained on high dose opioids and could explain why increasing the opioid dose paradoxically seems to result in poorer pain control than would be predicted. Paradoxically reducing the opioid dose may result in better pain management in this situation but, if suspected, seek specialist advice.
  • If the patient is on buprenorphine, in addition to splitting the dose (see above), and when an opioid is indicated consider:
    • Continuing to administer buprenorphine maintenance therapy and titrate a short-acting opioid analgesic to effect. As higher doses of full opioid agonist analgesics may be required caution should be taken if the patient's buprenorphine therapy is abruptly discontinued and with respect to CNS depression OR
    • Discontinue buprenorphine and titrate to a maintenance dose of methadone as an opioid substitution treatment. The pain may then be treated with opioid analgesics in addition to the oral substitution treatment.

Seek specialist advice if in doubt (see Contacts)

  • Due to the complex nature of these interventions and the potential for diversion of psychoactive prescription medications, clinicians should consider issuing smaller quantities and scheduling increased appointments to monitor use and efficacy of the pain management plan.
  • Indications of instability in substance use (both licit and illicit) should prompt a review of treatment and/or further discussion with the addiction services, pain clinic or both (if appropriate). Indicators for instability may include increased substance use (including alcohol), increased use of prescription medication including early requests for prescriptions, missing appointments, requests for replacement prescriptions when they have been lost or stolen and a change in behaviour on presentation.
  • Four common misconceptions which may result in under treatment of acute and chronic pain in substance users are:
    • Maintenance opioid agonists provide adequate analgesia (this is not so as duration of analgesia action [4-8hrs] is substantially shorter than that required for suppression of opioid withdrawal [24-48hrs]).
    • The use of opioid for analgesia may trigger relapse (the reverse is true acute pain is a well recognised potential trigger for relapse).
    • The additive effects of opioid analgesics and maintenance opioids may increase the likelihood of respiratory and CNS depression (this is not true when pain is present).
    • The pain complaint may simply be a manifestation of drug seeking behaviour (experience teaches that this is rarely so).

Remember: Addiction Services are available to advise and/or assess patients with complex presentations in addition to local pain clinics. Clinicians may either phone for advice or refer patients to the specialist service using the appropriate route:

Plymouth Specialist Addiction Service

  • First Floor, Hyde Park House, Mutley Plain, Plymouth. PL4 6LF
  • 01752 435222
  • Referral Mechanism: write to Medical Secretary

Plymouth Chronic Pain Management Team (chronic pain for over three months)

  • Erme House, Mount Gould Hospital, 200 Mount Gould Road, Plymouth, Devon PL4 7PY
  • 01752 437707
  • Usual referral mechanism for Chronic Pain Management Team

Torbay Primary Care Substance Misuse Service (TPCSMS)

  • Walnut Lodge, Walnut Road, Torquay TQ2 6HP
  • 01803 604330
  • Via open access sessions at various locations throughout the week across Torbay

Devon Partnership Trust – Drug and Alcohol Service

  • Shrublands House, 8 Morgan Avenue, Torquay, TQ2 5RS
  • 01803 291129
  • Bakers Hill, Newton Abbot, Devon, TQ12 1YP
  • 01626 351144

Torbay Chronic Pain Management Team (chronic pain for over 3 months)

  • Pain Clinic Secretaries, Chapel Corridor, Torbay Hospital, Lawes Bridge Road, Torquay. TQ2 7AA
  • 01803 654251 or 654270
  • Usual referral mechanism for Chronic Pain Management Centre


  1. The British Pain Society. Pain and Substance Misuse: improving the patient experience. April 2007. Available at **PLEASE NOTE THIS GUIDELINE IS CURRENTLY UNDER REVIEW AS OF NOVEMBER 2013

Useful resources

Opioids Aware: A resource for patients and healthcare professionals to support prescribing of opioid medicines for pain


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