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)

For support when prescribing opioids please refer to Opioids Aware: a resource for patients and healthcare professionals to support prescribing of opioid medicines for pain.

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
• The formulary has additional guidance supporting the recommendations from this review (See Management of Opioids)

Guidance on the use of opioids in palliative care can be found here.

• All slow release opioids should be prescribed by brand name.
• Specific dosage instructions should be written on the prescription, i.e. "X to be taken x hourly when required for pain", rather than simply "PRN". This ensures a maximum dose is stated and will prevent dose escalation without prescriber approval.

Renal impairment

Renal impairment alters the clearance of parent opioid compounds and also affects the accumulation of metabolites. This varies for individual opioids; an understanding of the pharmacokinetics of each drug is important to minimise the risk of toxicity. Refer to the BNF, individual Summary of Product Characteristics (SPC) and local specialists for further guidance.

The BNF recommends that the use of opioids in patients with hepatic impairment should be avoided or the dose reduced; opioids may precipitate coma in patients with hepatic impairment.

Weak Opioids

Compound preparations containing paracetamol and codeine can be found here

Codeine phosphate

• Tablets 15mg, 30mg, 60mg (£1.13 = 30mg x 28 tablets)
• Oral solution 25mg/5ml (£6.64 = 500ml)

Indications and dose

• Mild to moderate pain in adults
  • 30–60mg every 4 hours when necessary, to a maximum of 240mg daily
• Acute diarrhoea in adults (second line)
  • 30mg 3-4 times a day; dose range 15-60mg 3-4 times a day.

Notes

1. Codeine is useful for the relief of mild to moderate pain but is too constipating for long-term use.
2. The capacity to metabolise codeine to morphine can vary considerably between individuals; there is a marked increase in morphine toxicity in patients who are ultra-rapid codeine metabolisers, and a reduced therapeutic effect in poor codeine metabolisers. Prescribers should counsel patients on the symptoms of opioid toxicity prior to prescribing codeine and review patients shortly after initiating treatment. If no beneficial analgesic effect, treatment should be discontinued and alternative options discussed with the patient.

Strong Opioids

Morphine sulfate

• Oral solution 10mg/5ml (£8.49 = 300ml)
• Tablets 10mg, 20mg, 50mg (£10.61 = 20mg x 56 tablets)
• Orodispersible tablets sugar free 1mg, 2.5mg, 5mg, 10mg, 20mg, 30mg (£9.50 = 20mg x 56 tablets)
• Zomorph modified-release capsules 10mg, 30mg, 60mg, 100mg, 200mg (£8.30 = 30mg x 60 capsules)
• Solution for injection 10mg/1ml, 15mg/1ml, 20mg/1ml, 30mg/1ml (£48.44 = 30mg/1ml x 10 ampoules)
• Concentrated oral solution sugar free 100mg/5ml (£19.50 = 120ml)
• Intravenous infusion 50mg/5ml

Indications

• Acute pain
• Chronic pain
• Palliative care

Dose

• Acute pain (adult doses, for children refer to current BNFc and SmPCs)
  • By subcutaneous injection (not suitable for oedematous patients) or by intramuscular injection, initially 10mg (elderly or frail 5mg) every 4 hours or more frequently during titration), adjusted according to response
  • By slow intravenous injection, initially 5mg (reduce dose in elderly or frail) every 4 hours (or more frequently during titration), adjusted according to response
• Chronic pain (adult doses, for children refer to current BNFc and SmPCs)
  • By mouth or by subcutaneous injection (not suitable for oedematous patients) or by intramuscular injection, initially 5–10mg every 4 hours, adjusted according to response
• Zomorph 12 hourly modified-release (MR) capsules:
  • Every 12 hours, dose adjusted according to daily morphine requirements
  • For breakthrough, doses of 1/6 of the total daily dose of M/R opioid given as immediate-release morphine 4-hourly when required
  • During titration any increase in total daily opioid dosage should not be more than 50% of the previous total daily dosage

Notes

1. Prescribe modified-release preparations by brand. Modified-release (MR) preparations are available as 12-hourly or 24-hourly formulations; prescribers must ensure that the correct preparation is prescribed. Dosage requirements should be reviewed if the brand of morphine MR is altered. The pharmacokinetic profiles of MR products differ; to minimise the risk of mistakes, it is best to keep individual patients on the same MR brand. Including the brand name on the prescription and dispensing label will aid in identification of the correct formulation to be dispensed or administered.
2. Zomorph is the morphine sulfate MR preparation of choice - for patients who cannot swallow Zomorph capsules, their contents can be administered directly in semi-solid food (puree, jam, yoghurt) or via gastric or gastrostomy tubes of a diameter of more than 16 F.G. MST lacks these advantages and is more expensive than Zomorph and so its use is not recommended
3. Modified-release opioids (M/R) should only be used for constant, persistent, moderate to severe pain lasting several weeks and unlikely to resolve suddenly
4. Injectable opioids should not be used in the management of patients with persistent non-cancer pain
5. Caution, morphine sulfate oral solution may contain alcohol. This may be harmful for those suffering from a history of alcohol dependence and should be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy. Refer to individual Summary of Product Characteristics
6. Morphine sulfate oral solution should never be prescribed "when required" without a prescribed dose and dose interval
7. Following titration (except for stat doses e.g. for dressing changes) immediate release morphine should be given regularly every four hours. If pain recurs it is likely that increased dose or frequency of analgesia may be needed to regain pain control
8. Supplies of naloxone injection 400micrograms/1ml are required in the same clinical storage locations where morphine injections are stored, including in GPs' bags and bags held by out-of-hours providers (NPSA Safer Practice Notice 12; May 2006)

Diamorphine hydrochloride

• Injection 5mg, 10mg, 30mg, 100mg (£16.52 = 30mg x 5 ampoules)
• Do not start new patients on diamorphine hydrochloride 5mg or 10mg injection. National stock shortage. Review patients currently receiving diamorphine 5mg and 10mg injection. For more information, see the Medicines Optimisation Post Live article

Indications

• Acute pain
• Palliative care

Dose

• Acute pain, by subcutaneous or intramuscular injection, 5mg repeated every 4 hours if necessary (up to 10mg for heavier well-muscled patients); by slow intravenous injection, quarter to half corresponding intramuscular dose
• Chronic cancer pain, by subcutaneous or intramuscular injection
  • Adult not currently treated with a strong opioid analgesic, initially 2.5–5mg every 4 hours, adjusted according to response
  • Adult, by subcutaneous infusion, not currently treated with a strong opioid analgesic, initially 5–10mg over 24 hours, adjusted according to response
  • Adult currently treated with a strong opioid analgesic, see here for a table of approximate equivalent dosages of opioids

Notes

1. Injectable opioids should not be used in the management of patients with persistent non-cancer pain.
2. Supplies of naloxone injection 400 micrograms in 1ml are required in the same clinical storage locations where diamorphine injections are stored, including in GPs' bags and bags held by out-of-hours providers (NPSA Safer Practice Notice 12; May 2006).

Sevodyne

(Buprenorphine)

• Transdermal patch 5microgram/hour for 7 days (£5.53 = 4 patches)
• Transdermal patch 10microgram/hour for 7 days (£9.93 = 4 patches)
• Transdermal patch 15microgram/hour for 7 days (£15.48= 4 patches)
• Transdermal patch 20microgram/hour for 7 days (£18.09 = 4 patches)

Indications

• Moderate, non-malignant pain unresponsive to non-opioid analgesics

Dose

• Initially one '5micrograms/hour' patch; apply to dry, non-irritated, non-hairy skin on upper torso, removing after 7 days and siting replacement patch on a different area (avoid same area for at least 3 weeks)
• Analgesic effect should not be evaluated until the system has been worn for 72 hours (to allow for gradual increase in plasma-buprenorphine concentration)—if necessary, dose should be adjusted at intervals of at least 3 days using a patch of the next strength or a combination of 2 patches applied in different places (applied at same time to avoid confusion). Maximum 2 patches can be used at any one time (up to a maximum total dose of 40microgram/hour).

Notes

1. Prescribe by brand. Buprenorphine patches are available as 72-hourly (non-formulary), 96-hourly (non-formulary) and 7-day formulations. Brand name prescribing is recommended to reduce the risk of confusion and error in dispensing and administration.
2. High strength buprenorphine patches (e.g. Transtec, non-formulary) are not recommended for use.
3. If considering buprenorphine patches for patients with swallowing difficulties, remember that Zomorph capsules can be opened up for ease of swallowing.
4. Buprenorphine patches are not suitable, or licensed, for use in the management of acute or intermittent pain.
5. Prescribers should ensure that patients and/or their carers are aware that Sevodyne patches need to be applied at appropriate seven-day intervals to ensure that patients are not left in pain (because of too long an interval) and that the patches are not used wastefully (because of too short an interval). Remember to remove the old patch before application of new patch.
6. After removal of the patch, buprenorphine serum concentrations decrease gradually and thus the analgesic effect is maintained for a certain amount of time. This should be considered when therapy with Sevodyne is to be followed by other opioids. As a general rule, a subsequent opioid should not be administered within 24 hours after removal of the patch.
7. While wearing the patch, patients should be advised to avoid exposing the application site to external heat sources, such as heating pads, electric blankets, heat lamps, sauna, hot tubs, and heated water beds, etc., as an increase in absorption of buprenorphine may occur. When treating febrile patients, one should be aware that fever may also increase absorption resulting in increased plasma concentrations of buprenorphine and thereby increased risk of opioid reactions.
8. Buprenorphine sublingual tablets are not recommended for prescribing in primary care for the management of pain. For their use as an adjunct in the treatment of opioid dependence, refer to section 4.10.3 Opioid dependence.

Butec (existing patients only)

(Buprenorphine)

• Transdermal 7-day patch: 5microgram/hour (£7.92 = 4 patches); 10microgram/hour (£14.20 = 4 patches); 15microgram/hour (£22.12 = 4 patches); 20microgram/hour (£25.86 = 4 patches)
  • Butec patches have been removed from the formulary due to their high acquisition cost in comparison to Sevodyne patches. No new patients should be prescribed Butec patches. For existing patients, continued prescribing is accepted until the next review when the patient should be switched to Sevodyne transdermal patches if continuation of treatment is required.

Transdermal Fentanyl

• Opiodur patch 12microgram/hour, for 3 days (per patch £1.13)
• Opiodur patch 25microgram/hour, for 3 days (per patch £1.61)
• Opiodur patch 50microgram/hour, for 3 days (per patch £3.02)
• Opiodur patch 75microgram/hour, for 3 days (per patch £4.21)
• Opiodur patch 100microgram/hour, for 3 day (per patch £5.19)

Indications

• Severe chronic pain in patients with renal failure, morphine intolerance or poor compliance such as due to swallowing difficulties

Dose

• Adult and child over 2 years currently treated with a strong opioid analgesic, initial dose based on previous 24-hour opioid requirement.
• Apply to dry, non-irritated, non-irradiated, non-hairy skin on torso or upper arm, removing after 72 hours and siting replacement patch on a different area (avoid using the same area for several days)
• The initial evaluation of the analgesic effect of fentanyl patch should not be made until the patch has been worn for 24 hours due to the gradual increase in serum fentanyl concentration up to this time. Prescribers should consult individual product literature when titrating dose.

Notes

1. It is recommended that prescribers discuss the initiation of transdermal fentanyl with a pain specialist.
2. Prescribe by brand. Brand name prescribing is recommended to ensure continuity, and to reduce the risk of confusion and error in dispensing and administration.
3. Refer to specialist prior to increasing the dose beyond 25microgram/hour. A 25 microgram/hour patch of fentanyl is equivalent to approximately 60-90mg/24 hours of oral morphine (using a dose conversion ratio for morphine to fentanyl of 100-150:1). Doses above 25 microgram/hour are not recommended in the long term treatment of non-malignant pain (> 3 months).
4. Doses should be regularly reviewed and stepped down as soon as possible.
5. Prescribers should consult product literature and/or seek specialist advice when considering a switch to an alternative opioid.
6. Do not use in opioid naïve patients. Fentanyl patches should only be used in patients who are opioid tolerant and have already tried a strong opioid such as morphine. Fentanyl patches are implicated in a high level of patient harms and the CQC Annual Report for 2012 highlights the care that must be taken to ensure the safe use of these patches.
7. Do not use fentanyl patches for acute or intermittent pain.
8. Ensure that patients and/or their carers are aware that fentanyl patches need to be applied at appropriate 72-hour (three-day) intervals to ensure that patients are not left in pain (because of too long an interval) and that the patches are not used wastefully (because of too short an interval). Remember to remove the old patch before application of new patch. If patient is still experiencing pain in 72 hour change interval, review analgesia options. Do not suggest the patches are changed more frequently.
9. Patches should not be cut.
10. Despite the limited evidence and concerns regarding drug accumulation, fentanyl is a preferred opioid in renal impairment due to its inactive and non-toxic metabolites. It is nevertheless advisable to monitor for signs of opioid toxicity in these patients due to wide inter-patient variability.
11. MHRA Drug Safety Update 2008: Serious and fatal overdose of fentanyl patches
    1. Healthcare professionals, particularly those who prescribe and dispense fentanyl patches, must fully inform patients and caregivers about directions for safe use.
    2. Increased body temperature (e.g. fever), exposure of patches to external heat sources (e.g. hot bath or sauna), and concomitant use of CYP3A4 inhibitors may lead to potentially dangerous rises in serum fentanyl levels (examples include: ritonavir, nelfinavir, ketoconazole, itraconazole, clarithromycin, erythromycin, verapamil, diltiazem, and amiodarone) - concomitant use of other CNS depressants might also potentiate adverse effects from fentanyl.
    3. Healthcare professionals, particularly those who prescribe and dispense fentanyl patches, should ensure that patients and caregivers are aware of the signs and symptoms of fentanyl overdose—i.e. trouble breathing or shallow breathing; tiredness; extreme sleepiness or sedation; inability to think, walk, or talk normally; and feeling faint, dizzy, or confused - patients and caregivers should be advised to seek medical attention immediately (by dialling 999 and requesting an ambulance) if overdose is suspected.
    4. Patients who experience serious adverse events should have the patches removed immediately and should be monitored for up to 24 hours after patch removal.
12. MHRA Drug Safety Update (December 2014) and MHRA Drug Safety Update (October 2018): Transdermal fentanyl patches: life threatening and fatal opioid toxicity from accidental exposure, particularly in children
    1. Provide clear information to patients and caregivers regarding risk of accidental patch transfer and ingestion of patches, and need for appropriate disposal of patches.
    2. If a patch is transferred to another person, it should be removed and the individual should get medical help immediately.
    3. If a patch is swallowed, the individual should get medical help immediately.
    4. The 2014 drug safety update includes a letter for patients and care givers.
13. MHRA Drug Safety Update (September 2020): Transdermal fentanyl patches for non-cancer pain: do not use in opioid-naïve patients
    1. Remind patients that long-term use of opioids in non-cancer pain (longer than 3 months) carries an increased risk of dependence and addiction, even at therapeutic doses (see Drug Safety Update on risk of dependence and addiction with opioids);
    2. Before starting treatment with opioids, agree with the patient a treatment strategy and plan for end of treatment.
14. Refer to Section 16.2 Pain control in Palliative Care, Transdermal opioids for prescribing support in palliative care.

Matrifen and Mezolar (existing patients only)

(Fentanyl transdermal patch)

• Matrifen and Mezolar transdermal 3-day patch: 12microgram/hour (£1.50 per patch); 25microgram/hour (£2.15 per patch); 37.5microgram/hour (Mezolar only, £3.09 per patch); 50microgram/hour (£4.02 per patch); 75microgram/hour (£5.61 per patch); 100microgram/hour (£6.91 per patch)
  • Matrifen and Mezolar patches have been removed from the formulary due to their high acquisition cost in comparison to Opiodur patches. No new patients should be prescribed Matrifen or Mezolar patches. For existing patients, continued prescribing is accepted until the next review when the patient should be switched to Opiodur transdermal patches if continuation of treatment is required.

Oxycodone

• Shortec capsules 5mg, 10mg, 20mg (£20.58 = 30mg daily)
• Longtec modified-release tablets (12 hourly dosing) 5mg, 10mg, 15mg, 20mg, 30mg, 40mg, 60mg, 80mg, 120mg (£37.57 = 40mg daily)
• Oral solution sugar free 5mg/5ml (£7.97 = 250ml)
• Solution for injection 10mg/1ml, 50mg/1ml (£2.65 = 10mg/1ml ampoule)

Indications

• Moderate to severe pain in patients intolerant to morphine

Dose

• Oral immediate-release, initially 5mg every 4–6 hours, increased if necessary according to severity of pain, usual maximum 400mg daily, but some patients may require higher doses (note: 400mg oral oxycodone is approximately equivalent to 800mg oral morphine)
• Oral modified-release, initially 10mg every 12 hours, increased if necessary according to severity of pain, usual maximum 200mg every 12 hours, but some patients may require higher doses (note: 200mg oral oxycodone is approximately equivalent to 400mg oral morphine)
• Slow intravenous injection, 1–10mg every 4 hours when necessary
• Intravenous infusion, initially 2mg/hour, adjusted according to response
• Subcutaneous injection, initially 5mg every 4 hours when necessary
• Subcutaneous infusion, initially 7.5mg/24 hours adjusted according to response

Notes

1. Prescribe oral preparations by brand. Oral oxycodone modified-release preparations are available in 12-hourly and 24-hourly (non-formulary) formulations. Oral oxycodone immediate-release preparations are available as capsules and tablets (non-formulary) formulations. Brand-name prescribing is recommended to reduce the risk of confusion and error in dispensing and administration.
2. Oxycodone cannot be recommended as a replacement for morphine in the step-wise management of pain, but could be considered an alternative for patients who cannot tolerate morphine.
3. Increasing doses above 240mg oral oxycodone (or equivalent) / 24hours is unlikely to yield further benefits and exposes the patient to increased harm.
4. May be used with caution in patients with renal impairment: starting dose should be reduced by 50%. The dose should be slowly titrated upwards depending on response and any observed adverse effects.
5. Injectable opioids should not be used in the management of patients with persistent non-cancer pain.
6. Oxycodone with naloxone combination product (Targinact, non-formulary) is not recommended for use locally. See entry below for further details.

Tramadol

• Capsules 50mg (£2.20 = 100 capsules)
• Solution for injection 100mg/2ml (£0.80 = 2ml ampoule)

Indications

• Moderate to severe pain

Dose

• Oral, 50–100mg not more often than every 4 hours; total of more than 400mg daily not usually required
• By intramuscular injection or by intravenous injection (over 2–3 minutes) or by intravenous infusion, 50–100mg every 4–6 hours
• Postoperative pain, 100mg initially then 50mg every 10–20 minutes if necessary during first hour to total maximum 250mg (including initial dose) in first hour, then 50–100mg every 4–6 hours; maximum 600mg daily

Notes

1. Modified-release preparations of tramadol are non-formulary. However, if there is a defined clinical need for a modified-release preparation, prescribe as 12-hourly brand product Marol to ensure lowest acquisition cost.
2. Tramadol may be useful if codeine is ineffective or not tolerated. Up to 20% of patients may not metabolise codeine efficiently to its active metabolite, morphine.
3. Caution: Tramadol increases CNS serotonin levels and may cause increased serotogenic effects when given with other drugs that increase serotonin levels e.g. SSRIs, SNRIs, MAOIs and some TCAs.
4. The use of Tramadol in patients with a history of epilepsy is not recommended unless compelling reasons, as there may be an increased risk of convulsions.
5. Injectable opioids should not be used in the management of patients with persistent non-cancer pain.
6. MHRA Drug Safety Update (June 2024): Warfarin: be alert to the risk of drug interactions with tramadol
   1. Be aware of the risk of increased INR when coumarin-derived anticoagulants and tramadol are used together, with a risk of major bruising and bleeding which could be life-threatening. Consider whether additional monitoring of INR is required when starting tramadol or another concomitant medicine.
   2. Refer to the safety update for advice to give to patients.

Abstral

(Fentanyl)

• Sublingual tablets 100micrograms, 200micrograms, 300micrograms, 400micrograms, 600micrograms, 800micrograms (£5.00 = per tablet)

Indications

• Breakthrough cancer pain not adequately treated with additional oral morphine in Palliative care

Dose

• Abstral requires dose titration to determine optimal dosage - consult product literature for further details.
• If more than 4 episodes of breakthrough pain each day, adjust background analgesia (and re-evaluate and re-titrate Abstral dose as necessary)

Notes

1. Do not prescribe for patients with non-cancer pain.
2. Prescribe by brand. The dose of Abstral is not interchangeable with other oramucosal fentanyl products available (Actiq and Effentora, both non-formulary) and patients must not have their preparations switched.
3. Following national guidance from NHS England, Abstral should only be used in patients undergoing palliative care treatment and where the recommendation to use immediate release fentanyl in line with NICE guidance, has been made by a multi-disciplinary team and/or other healthcare professional with a recognised specialism in palliative care.
4. Patients must be assessed by the palliative care or pain team before commencing treatment with Abstral tablets. They should only be used in the minority of patients with breakthrough cancer pain that fail immediate release morphine or oxycodone. Patients must be reviewed weekly.
5. Immediate-release oral morphine remains the preferred treatment for breakthrough pain in palliative care patients. When more rapid onset and briefer duration of action are of significant clinical importance the greater cost of Abstral may be justified for this group of patients.

Alfentanil

• Solution for injection 500micrograms/ml, 2ml ampoule (£6.34 x 10 ampoules)
• Solution for injection 5mg/ml, 1ml ampoule (£31.00 x 10 ampoules)

Indication

• Subcutaneous alfentanil may be used for end of life patients in renal failure (eGFR <30mL/minute/1.73m²), only under specialist advice

Notes

1. Refer to Chapter 16: Palliative Care for further guidance on the use of alfentanil.
2. Although not included in the original safety alert, the use of 5mg in 1ml amps is subject to the same restrictions as high strength morphine and diamorphine as per NPSA Safer Practice Notice 12; May 2006.

Subcutaneous fentanyl

• Solution for injection 100micrograms/2ml (£16.24 = 10 x 2ml ampoules)

Indication

• Subcutaneous fentanyl may be used for end of life patients in renal failure (eGFR <30mL/minute/1.73m²), only under specialist advice

Notes

1. Refer to Chapter 16: Palliative Care for further guidance on the use of subcutaneous fentanyl.

Tapentadol

• Immediate-release tablets 50mg, 75mg (£99.68 = 50mg x 224 tablets)
• Modified-release tablets 50mg, 100mg, 150mg, 200mg, 250mg (£99.64 = 200mg x 56 tablets)
• Oral solution sugar free 20mg/ml (£99.68 = 400mg/24 hours)

Dose and Indications

• For use in patients with severe pain who are intolerant to morphine
• Immediate-release for the treatment of acute pain:
  • 50 mg every 4–6 hours, adjusted according to response; usual maximum 600mg daily
• Modified-release for the treatment of chronic pain:
  • 50mg every 12 hours, adjusted according to response; maximum 500mg daily

Notes

1. Only to be initiated by a pain specialist or rheumatologist.
2. May cause less GI adverse effects than other strong opioid analgesics.
3. 50mg tapentadol has approximate analgesic equivalence to 20mg morphine, and to 10mg oxycodone. These ratios reflect analgesic efficacy and not opioid activity. Since a proportion of tapentadol's analgesic activity comes noradrenaline reuptake inhibition there is a risk of opioid withdrawal problems if a direct switch is made from morphine or oxycodone. To avoid such problems local specialists recommend adding a dose of tapentadol to the patient's existing regimen, followed by a gradual reduction of opioid medication over at least two weeks.
4. MHRA Drug Safety Update (January 2019): Tapentadol (Palexia): risk of seizures and reports of serotonin syndrome when co-administered with other medicines
   1. As for all opioid medicines, tapentadol can induce seizures.
   2. Tapentadol should be prescribed with care in patients with a history of seizure disorders or epilepsy.
   3. Tapentadol may increase seizure risk in patients taking other medicines that lower seizure threshold, for example, antidepressants such as serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants, and antipsychotics.
   4. Serotonin syndrome has been reported when tapentadol is used in combination with serotoninergic antidepressants.
   5. Withdrawal of the serotoninergic medicine, together with supportive symptomatic care, usually brings about a rapid improvement in serotonin syndrome.

Oxycodone and naloxone combination product (Targinact)

Following national guidance from NHS England, this product is not recommended for use due to the significant cost of the oxycodone and naloxone combination product and the unclear role of the combination product in therapy compared with individual products. Click here for more information. Prescribers should not initiate oxycodone and naloxone combination product for any new patient.