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4.7.1 - 4.7.2 Non-opioid & opioid analgesics

Guidelines for the management of neuropathic pain in primary care

Non-malignant chronic pain in primary care

 Trust Chronic pain guidelines 

Oral loading doses of paracetamol in adults prior to surgery

Acute pain management of adults already receiving opioids prior to surgery

Choice of strong opioids for cancer pain

4.7.1 Non-opioid analgesics

*Refer to Section 10 for non-steroidal inflammatory agents*
Paracetamol tablets, soluble tablets, oral suspension (sugar-free), suppositories, intravenous infusion
Aspirin dispersible, enteric coated tablets, suppositories
Co-codamol 8/500 tablets, dispersible tablets
Co-dydramol 10/500 tablets
Nefopam tablets, injection - see note

Notes:

1. The use of combination analgesics containing high-strength codeine or dihydrocodeine (e.g. cocodamol 30/500 [Kapake, Tylex, Solpadol]) does not allow flexibility of administration and will lead to constipation. These products are excluded from the Formulary and should be prescribed separately.

2. Co-proxamol (Distalgesic) was removed from the market in 2005. No new patients will be commenced on this drug.

3. Guidelines for oral and IV dosing of paracetamol in ADULTS

Paracetamol has a narrow therapeutic index. Serious toxicity is unlikely in most patients ingesting less than 150 mg/kg if taken over any 24 hour period. Less commonly, toxicity can occur with doses between 75 and 150 mg/kg over 24 hours in some patients. Several case reports and one prospective study have reported acute liver failure secondary to therapeutic doses of oral paracetamol in patients with identifiable risk factors for liver toxicity. As there is no formal guidance for adjusting the dose of oral paracetamol in patients with identifiable risk factors, the oral doses recommended in this guideline are based upon a maximum daily dose of 75mg/kg, given liver toxicity may develop at doses this low in patients at high-risk of liver-damage taken within 24 hours. The doses have then been rounded to the nearest 500mg dose for ease of prescribing and administration. Patients who require a dosage adjustment should be advised that this will be lower than the maximum dose of paracetamol recommended in package inserts.

Intravenous dosing
Intravenous paracetamol should only be used when the oral route is not available. It can be used in preference to the rectal route where appropriate as the rectal route has unpredictable bioavailability, and is more expensive.
Intravenous administration of paracetamol results in higher peak plasma levels than the same dose given orally. The product license specifies that the standard maximum daily dose of 4g daily must be decreased in patients with a body weight ≤50kg (to 15 mg/kg per dose) or in those with risk factors for toxicity (see chart below). The dosing interval needs to be increased in patients with severe renal impairment.

Risk factors for hepatotoxicity
Malnourished patients, with nutritional deficiency and/or chronic debilitating illness are likely to be glutathione deplete e.g. acute (patients not eating for a few days) or chronic starvation, eating disorders (anorexia or bulimia), cystic fibrosis, AIDS, cachexia, alcoholism, Hepatitis C. Hepatic enzyme induction or evidence of on-going liver injury e.g. long term treatment with liver enzyme-inducing drugs such as carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, rifabutin, efavirenz, nevirapine, St John's Wort; regular consumption of ethanol in excess of recommended amounts, particularly if nutritionally compromised.

Dose adjustment of paracetamol in adults  
1. Record patient weight on drug chart.
2. Assess the patient for risk factors for toxicity.
3. If risk factors are present REDUCE the total daily dose.
4. Prescribe the oral dose in multiples of 500mg of paracetamol.
5. Do not exceed four doses of paracetamol in 24 hours

 

Dose of ORAL paracetamol in ADULT patients WITHOUT risk factors

 500mg-1g every 4-6 hours
Maximum 4g daily

 

 

 

Recommended dose adjustment of ORAL paracetamol in ADULT patients WITH risk factors

   

30- 39kg                  

40 - ≤ 50kg  

 

> 50kg  

 

Dose reduction is required. Final dose to be determined on an individual basis. (Consult a senior clinician/ pharmacist for advice)

500mg-1g every 4-6 hours
Maximum 3g daily


500mg-1g every 4-6 hours
Maximum 4g daily

 

 

Dose of IV paracetamol in ADULTS

 ≤33kg with or without risk  factors

15mg/kg per dose every 4-6 hours
Maximum 2g daily

 >33 - ≤50kg with or without risk factors

15mg/kg per dose every 4-6 hours
Maximum 3g daily

 >50kg with risk factors

1g every 4-6 hours
Maximum 3g daily

 >50kg and no risk factors

1g every 4-6 hours
Maximum 4g daily

 Renal function GFR<30ml/min

Dose according to weight and risk factors but increase the minimum dosing interval to 6 hours

 

4. Guidelines on administration of paracetamol in CHILDREN

 Click here for guidelines

5. Vigilance is advised when prescribing and administering intravenous paracetamol 10 mg/mL solution for infusion to ensure that the correct dose is given. For all patients, dose requirement is based on weight as outlined below and
in the product information. For infants and children who weigh less than 33 kg, the 50 mL vial should be used for administration.

6. Note that irrespective of dose, the dosing schedule is up to four infusions a day with a minimum of 4 hours between each administration (6 hours for those with renal impairment).


Term newborn infants, toddlers and children weighing <10 kg Children weighing >10kg and <33kg Children, adolescents and adults weighing >33kg and <50kg Adolescents and adults weighing >50kg
Dose (per administration) One intravenous infusion of 7.5mg/kg: i.e. 0.75ml solution per kg One intravenous infusion of 15mg/kg: i.e. 1.5ml solution per kg One intravenous infusion of 15mg/kg: i.e. 1.5ml solution per kg One intravenous infusion of 1g: i.e. 100ml solution
Maximum daily dose 30mg/kg (i.e. 3ml/kg) 60ml/kg (i.e. 6ml/kg) without exceeding 2g (i.e. 200ml) in total 60ml/kg (i.e. 6ml/kg) without exceeding 3g (i.e. 300ml) in total Must not exceed 4g (i.e. 400ml) in total


 Note: maximum daily dose in each dose range refers to that for maximum weight in each range.

7. Because of its high cost and poor evidence base, nefopam has been classified as BLACK by the local CCG i.e. “not routinely recommended or commissioned”- based on: Lack of data on effectiveness compared with standard therapy; Lack of data on safety compared with standard therapy; Less cost-effective than current standard therapy. Therefore, no new patients should be initiated on this treatment, and existing patients should be reviewed and changed to a more suitable alternative

4.7.2 Opioid analgesics

This advice relates to the use of strong opioids (and weak opioids at doses higher than recommended in BNF) for persistent pain.

Cautions

  • The safety and efficacy of long term opioid use is uncertain (there are few trial data for use more than 12 weeks), although use may be appropriate in some cases of persistent pain (somatic, visceral or neuropathic).
  • Local and national prescribing guidance should be followed carefully.
  • Medication for pain should be used only as part of a wider management plan aimed at reducing disability and improving quality of life.
  • Opioids should not usually be used as first line therapy for pain.
  • Opioids should not be used in children or pregnant women without specialist advice, and they should be used with caution in older people (particularly those with medical co-morbidity).
  • Patients with a history of addiction to opioids or other drugs need referral to services with expertise in pain medicine and addiction management.
  • Patients should not drive when starting opioids or adjusting dose or if they feel unfit to drive.

 

    Prescribing
  • Comprehensive assessment is important; patients with depression, anxiety, or other psychiatric or psychological co-morbidity will need additional support and monitoring to avoid problem drug use.
  • Goals of therapy should be agreed before a trial of opioids; complete pain relief is unlikely, and treatment success is demonstrated by the patient becoming able to do things that the pain currently prevents. Treatment should be reviewed at least monthly, more often if there are any concerns.
  • Start with a low dose and titrate up according to analgesia and side effects. Doses greater than 180 mg morphine daily (or equivalent) require specialist advice.
  • Where possible use regular dosing with modified release preparations; immediate release opioids may be associated with tolerance and problem drug use.
  • Efficacy and adverse effects are similar for all opioids, though patients may tolerate one drug better than another.
  • Requests for dose increase need careful evaluation.
  • NEVER prescribe opioid injections, or pethidine in any form, for the management of persistent non cancer pain (unless on the advice of a specialist pain management team).
  • If care is shared between hospital and community, be clear who is responsible for prescribing. Within the GP practice, only one clinician should be signing repeat opioid prescriptions. Acute prescriptions may be safer if there are concerns.

 

Adverse effects

  • 80% of patients taking opioids will experience at least one adverse effect e.g. constipation, nausea, itching, dizziness. Side effects should be managed promptly with laxatives, anti-emetics etc as appropriate.
  • Opioid toxicity (sedation, slow respiration, cyanosis) is more likely with increasing age, co-morbidity, co-prescribing, and if opioids are taken with alcohol or illicit drugs.
  • Opioids have long term endocrine and immunological effects.
  • Withdrawal symptoms occur if opioid is stopped/dose reduced abruptly e.g. sweating, yawning, abdominal cramps. This is common with Tramadol even after a short course.
  • Addiction is characterised by impaired control over use, craving and continued use despite harm.
  • Opioid induced hyperalgesia may occur: pain becomes more diffuse and qualitatively different from pre-existing pain. Specialist advice is needed.


Click here for the full version of the Opioids for persistent pain: Good Practice

Click here for NICE Clinical Guideline: Opioids in palliative care: safe and effective prescribing of strong opioids for pain in palliative care of adults 

ORAL

*CD* Buprenorphine Sublingual tablets (see note 5)
Codeine Phosphate  tablets, elixir - see note regarding new restrictions on use of codeine in children/adolescents
Dihydrocodeine tablets, oral solution
*CD* Morphine Sulphate MR capsules (Zomorph); if required, MST 5mg may occasionally be used to facilitate dosing 
Morphine Sulphate oral solution 10mg/5mL (Adults)
Morphine Sulphate oral solution 500 micrograms/1mL (NICU)
*CD* Morphine Sulphate oral solution (sugar free) 20mg/1mL (Palliative care only)
*CD* Morphine Sulphate tablets (Sevredol)
*CD* Phenazocaine tablets (for hepato biliary disease)

*CD* Oxycodone M/R Tablets (Oxycontin) See note

*CD* Oxycodone Immediate Release Capsules (Oxynorm) - see note
Tapentadol (SR-form) - specialist use in pain clinic for patients intolerant of morphine or oxycodone
Tramadol tablets- for use by the pain team as per the neuropathic pain guidelines.

Note; in June 2014 Tramadol was reclassified as a Controlled Drug (CD Schedule 3). Click here for further information and here for a stock / named requisition form. 

 

PARENTERAL

Alfentanil injection (s/c infusion in palliative care - patients with poor renal function (eGFR < 30ml/min only)
*CD* Codeine Injection
*CD* Diamorphine injection - see note re end-of-life care
*CD* Diamorphine intrathecal 300micrograms/0.3ml, epidural 2.5mg/10ml.
*CD* Dihydrocodeine
*CD* Pethidine injection
*CD* Morphine sulphate injection
*CD* Morphine + Cyclizine (Cyclimorph) injection
*CD* Oxycodone Injection - see note

 

PATCH

Fentanyl patch - see note

Notes:

1. Opioid requirements should be titrated according to response for individual patients.

2. Starting doses of 5 or 10mg of oral morphine are suggested.  Duration of effect is approximately four hours.  A few patients are particularly sensitive to the sedative effects of morphine and may require smaller doses.

3. A stimluant laxative should be prescribed whenever regular morphine is started.

4. Oral morphine is available both as a solution and as immediate release Sevredol tablets. When patients are pain controlled on a 4-hourly regimen they may be changed to 12-hourly slow release morphine (Zomorph).  Oral conventional release morphine preparations are approximately equipotent mg for mg with slow release morphine i.e. 180mg morphine over 24 hours as morphine 30mg 4-hourly is equivalent to 90mg slow release morphine 12-hourly.  It is recommended that sevredol and zomorph are prescribed by their trade names to prevent confusion and that particular care is taken over times of administration.

5. Following a European safety review, there are now restrictions on the use of codeine in children and adolecents, as well as in breast-feeding mothers.  See Drug Safety Update June 2013Drug Safety Update July 2013 ; Drug Safety Update April 2015. A memo from paediatrics outlining the local response to these safety alerts is available. Click for interim local guideline regarding use of codeine in children.  

6. Diamorphine is the opioid of choice for subcutaneous administration for breakthrough pain for palliative care patients. For further information on administration and dose equivalence please click here.

7. Fentanyl patches are NOT suitable for opioid naïve patients or those with acute pain.

One of the key errors that can occur is the unintended use of multiple patches simultaneously leading to opiate toxicity. This can be caused by not realising the patient has a patch in situ, or by failing to remove the old patch before applying a new one.
To act as a prompt, the EPMA entry for fentanyl and buprenorphine patches now contains a reminder to remove old patches.

The Medicines Safety Group have recently produced practical guidance on the prescribing and administration / disposal of fentanyl and buprenorphine patches

 

For link to BNF section: 4.7 Analgesics