Analgesia—mild-to-moderate pain

Which analgesics are available for the treatment of mild-to-moderate pain?

• The analgesics that are used to relieve mild-to-moderate pain are:
  • paracetamol
  • non-steroidal anti-inflammatory drugs (NSAIDs)—classified as standard NSAIDs (for example diclofenac, ibuprofen, indometacin, mefenamic acid, and naproxen) or coxibs (for example celecoxib, etoricoxib)
  • weak opioids (such as codeine, dihydrocodeine, and tramadol)
  • aspirin
• Fixed-dose combination preparations are also available, including:
  • paracetamol with codeine
  • paracetamol with dihydrocodeine
  • paracetamol with tramadol
  • aspirin with codeine.

Choice of analgesic

Which analgesic should I prescribe for children under 16 years of age?

• Prescribe either paracetamol or ibuprofen alone. Both are suitable first-line choices for treating mild-to-moderate pain in children
• If the child does not respond to the first analgesic:
  • check their adherence, and that an appropriate dose is being taken
  • if paracetamol has been used, switch to ibuprofen alone
  • if ibuprofen has been used, switch to paracetamol alone
• If the child has not responded sufficiently to appropriate doses of either drug alone, consider alternating paracetamol and ibuprofen
  • add a dose of the second drug (for example, 2–3 hours after the first drug), provided that the parents/carers are confident to do this
  • paracetamol is usually given every 6 hours and ibuprofen every 8 hours. Care needs to be taken not to exceed the maximum dose of each drug in a 24-hour period
  • a treatment diary may be useful if the parents or carers find it difficult to remember which was the last drug given and at what time
• If the child is still in pain or more than short courses of analgesics are required, consider seeking specialist advice
• The following treatment options are not recommended for children in primary care:
  • administering paracetamol and ibuprofen at the same time
  • naproxen
  • diclofenac
  • aspirin
  • weak opioids.

Which analgesic should I prescribe for people 16 years of age and older?

• A stepwise strategy for managing mild-to-moderate pain in adults is recommended:
  • step 1—paracetamol. This is a suitable first-line choice for most people with mild-to-moderate pain
    • increase to the maximum dose of 1 g four times a day, before switching to (or combining with) another analgesic
  • step 2—substitute the paracetamol with low-dose ibuprofen (400 mg three times a day). If necessary, increase the dose of ibuprofen to a maximum of 2.4 g daily, except where this is contraindicated (see the section on Contraindications)
    • if the person is unable to take a NSAID, use a full therapeutic dose of a weak opioid (such as codeine 60 mg every 4–6 hours; maximum 240 mg daily)
  • step 3—add paracetamol (1 g four times a day) to low-dose ibuprofen (400 mg three times a day). If necessary, increase the dose of ibuprofen to a maximum of 2.4 g daily
    • if the person is unable to tolerate an NSAID, add paracetamol to a weak opioid
  • step 4—continue with paracetamol 1 g four times a day. Replace the ibuprofen with an alternative NSAID (such as naproxen 250 to 500 mg twice a day)
  • step 5—start a full therapeutic dose of a weak opioid (such as codeine 60 mg up to four times a day; maximum 240 mg daily) in addition to full-dose paracetamol (1 g four times a day) and/or an NSAID.

General points to consider when prescribing analgesics

• The underlying cause of the pain should be treated whenever possible
• People who experience continuous pain should receive regular analgesia following a full clinical assessment
• Ensure a full therapeutic dose is used before considering switching to a different analgesic
• For people who are at an increased risk of gastrointestinal (GI) adverse effects, consider prescribing an alternative to an oral NSAID
  • if an NSAID is necessary, prescribe low-dose ibuprofen (400 mg three times a day) with a proton pump inhibitor. See the CKS topic on NSAIDs—prescribing issues for more information
• For people with underlying heart or circulatory conditions, prescribe low-dose ibuprofen (400 mg three times a day). Avoid doses of 2.4 g or more in this group of people
• Effervescent preparations should be avoided (due to their high salt content), particularly in people with hypertension
• Combination analgesics should be avoided as first-line treatment. Prescribing single-constituent analgesics allows independent titration of each drug.

Paracetamol

When is paracetamol indicated and what dose should I prescribe?

• Paracetamol is licensed for mild-to-moderate pain. It is a suitable first-line choice for most people with mild-to-moderate pain, and for combination therapy
  • for more information, see Choice of analgesic
• Doses of paracetamol for adults and children aged 16 years of age (18 years of age by rectum) and over are:
  • orally—500 mg—1 g every 4–6 hours (maximum 4 g in 24 hours)
  • by rectum—500 mg—1 g every 4–6 hours (maximum 4 g in 24 hours)
• Doses of paracetamol for children younger than and up to 16 years of age (18 years of age by rectum) are as follows. These doses may be repeated every 4–6 hours if necessary (maximum of four doses in 24 hours):

Oral dose:		By rectum:
Age	Dose	Age	Dose
3–6 months	60 mg	3–12 months	60–125 mg
6–24 months	120 mg	1–5 years	125–250 mg
2–4 years	180 mg	5–12 years	250–500 mg
4–6 years	240 mg	12–18 years	500 mg
6–8 years	250 mg
8–10 years	375 mg
10–12 years	500 mg
12–16 years	500–750 mg

What are the cautions and contraindications for paracetamol?

• There are no contraindications to the use of paracetamol
• Prescribe paracetamol with caution if there is alcohol dependence, chronic alcoholism, chronic malnutrition, or dehydration
• Caution is advised in people who weigh under 50 kg
• Hepatic impairment (see the full guideline for more information).

What are the adverse effects of paracetamol?

• Adverse effects are rare with paracetamol
  • there have been very rare reports of blood dyscrasias (including thrombocytopenia and agranulocytosis) in people taking paracetamol, but it is not clear that these were directly caused by the paracetamol
• However, paracetamol doses greater than the maximum daily dose of 4 g can lead to hepatotoxicity (and, less frequently, acute kidney injury). In some people this may be fatal
• People who have taken an overdose of paracetamol (accidentally or intentionally) may require urgent admission to hospital, depending on the quantity of paracetamol taken and the presence of risk factors for liver damage, including: alcohol dependence, pre-existing liver disease, malnutrition, and the use of liver enzyme inducing drugs (such as rifampicin, carbamazepine, and phenytoin)
• Early symptoms of paracetamol toxicity are nausea, vomiting, and abdominal pain which usually settle within 24 hours. Symptoms of liver damage include right subcostal pain and tenderness
• Liver damage peaks 3–4 days after paracetamol ingestion. The person may develop encephalopathy, haemorrhaging, hypoglycaemia, and cerebral oedema
• For advice on when admission is required, see the TOXBASE website or telephone the national Poisons Services on 0844 892 0111.

What are the key drug interactions with paracetamol and how should I manage them?

• Alcohol —for more information, see the CKS topic on Alcohol—problem drinking

Can I prescribe paracetamol to a woman who is pregnant, planning a pregnancy, or breastfeeding?

• Pre-conception and pregnancy
  • paracetamol is the analgesic of choice for women who are trying to conceive, or who are pregnant
  • it can be used at the standard dose at any stage of pregnancy
• Breastfeeding
  • paracetamol is suitable for use during breastfeeding
  • seek expert advice if the infant is pre-term, low birth weight, or if the absorption, distribution, metabolism, or excretion of paracetamol may be affected by an underlying medical condition in the infant.

What information and advice should I give to a person receiving paracetamol?

• Advise the person that:
  • if they have continuous pain, they should use paracetamol regularly (four times a day)
  • paracetamol rarely causes adverse effects when used at the correct dosage
  • there are other paracetamol-containing medicines available over the counter. The maximum total dosage of 4 g in 24 hours must not be exceeded.

Aspirin

When is aspirin indicated and what dose should I prescribe?

• Aspirin is a first-line option for the management of migraine—for more information, see the CKS topic on Migraine
• In most circumstances where analgesia is required, other NSAIDs (such as ibuprofen) are preferred to aspirin, because they are better tolerated
• Analgesic doses of aspirin for adults and children older than 16 years of age are:
  • by mouth—300–900 mg every 4–6 hours when necessary (maximum 4 g in 24 hours)
  • by rectum—450–900 mg every 4 hours (maximum 3.6 g in 24 hours).

What are the cautions and contraindications for aspirin?

• Do not prescribe aspirin to people with:
  • a history of true hypersensitivity to aspirin or salicylates
  • active bleeding (such as peptic ulcer or intracranial haemorrhage)
  • suspected stroke (until intracranial haemorrhage has been excluded by brain imaging)—see the CKS topic on Stroke and TIA for more information
  • haemophilia or other haemorrhagic disorders (including thrombocytopenia)
  • gout, or a history of gout—at analgesic doses, aspirin increases the level of uric acid
  • severe hepatic impairment
  • severe chronic kidney disease
  • children younger than 16 years of age (unless specifically indicated by a specialist, for example for Kawasaki disease)—due to the risk of Reye’s syndrome
  • women who are in the third trimester of pregnancy or who are breastfeeding—for more information, see the section on Pre-conception, pregnancy and breastfeeding.
• Prescribe aspirin with cautionin people with:
  • an increased risk of bleeding (see the section on Drug interactions)
  • uncontrolled blood pressure—do not initiate aspirin until the person’s blood pressure is less than 150/90 mmHg. For further information, see the CKS topic on Hypertension—not diabetic
  • asthma—for further information, see the CKS topic on Asthma.

What are the adverse effects of aspirin?

• GI irritation with slight asymptomatic blood loss is common
• Other less common adverse effects which have been reported include:
  • GI erosion and ulceration
  • nausea, vomiting, gastritis, and dyspepsia
  • increased bleeding time
  • bronchospasm and acute exacerbation of asthma in susceptible people
  • skin reactions in people who are hypersensitive to aspirin.

What are the key drug interactions with aspirin and how should I manage them?

• The risk of bleeding is increased when aspirin is combined with other drugs known to increase the risk of GI bleeding:
  • consider gastroprotection (for example with a proton pump inhibitor) if concurrent use of aspirin and the following drugs is indicated:
    • other NSAIDs, such as naproxen and ibuprofen
    • oral and parenteral anticoagulants (for example warfarin or heparin)—only initiate aspirin in people taking anticoagulants under specialist advice
    • selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors—consider switching to a different analgesic (such as paracetamol)
    • other drugs known to increase the risk of GI bleeding—for example corticosteroids and clopidogrel
  • for more information, see the CKS topic on NSAIDs—prescribing issues
• The toxicity of methotrexate may be increased by aspirin
  • the methotrexate dosage should be carefully monitored in people taking aspirin
  • this risk is considered to be greater in people receiving high doses of methotrexate (150 mg daily or more) and in those with chronic kidney disease.

Can I prescribe aspirin to a woman who is pregnant, planning a pregnancy, or breastfeeding?

• Pre-conception
  • paracetamol is the analgesic of choice for women who are trying to conceive
  • occasional single doses of aspirin are unlikely to affect conception rates. However, if the woman is having difficulty conceiving or is undergoing investigation for infertility, aspirin should not be taken for analgesia
  • for more information on the effects of aspirin on conception, contact the UK Teratology Information Service (UKTIS) on 0844 892 0909
• Pregnancy
  • paracetamol is the analgesic of choice for pregnant women
  • analgesic doses of aspirin are not known to be harmful when used during the first and second trimesters of pregnancy
  • avoid analgesic doses of aspirin during the third trimester of pregnancy (although low doses are used for prophylaxis against eclampsia in high-risk women—see the full guideline for further information)
• Breastfeeding
  • paracetamol is the analgesic of choice for women who are breastfeeding
  • do not prescribe analgesic doses of aspirin for women who are breastfeeding (see the full guideline for further information).

What information and advice should I give to a person receiving aspirin?

• Advise the person to:
  • take aspirin with or after food (to reduce the risk of GI adverse effects)
  • stop aspirin and seek medical advice if they experience bronchospasm or dyspepsia
  • seek advice from a healthcare professional (such as a pharmacist) before buying over-the-counter medicines. These might contain ingredients (for example ibuprofen) which can increase the risk of adverse effects from aspirin.

NSAIDs

Which NSAID should I prescribe?

• For detailed information on prescribing NSAIDs, see the NICE PRODIGY topic NSAIDs—prescribing issues.

Weak opioids

• Please refer to the full guideline for the complete set of recommendations.

What are the key drug interactions with weak opioids and how should I manage them?

• All weak opioids interact with:
  • central nervous system depressants—if possible, avoid concomitant use
  • monoamine oxidase inhibitors (MAOIs)—avoid concomitant use of a weak opioid with a MAOI, and avoid using weak opioids in the 2 weeks after stopping a MAOI
• Tramadol interacts with:
  • selective serotonin reuptake inhibitors
  • tricyclic antidepressants
  • carbamazepine
  • warfarin.

What information and advice should I give to a person receiving weak opioids?

• Advise the person:
  • on the common adverse effects of weak opioids (please refer to the full guideline for further information) including nausea and vomiting, drowsiness, unsteadiness, and constipation
    • a regular laxative is not usually needed for short-term use of weak opioids
  • about driving while taking weak opioids:
    • they should not drive if they feel drowsy, dizzy, unable to concentrate or make decisions, or if they experience blurred or double vision
    • it is now an offence to drive if they have more than a specified amount of opioid in their body whether driving is impaired or not. It may be helpful for the person to keep evidence (such as their repeat prescription) in the car to show that they are taking an opioid in accordance with medical advice
  • that weak opioids purchased over the counter should only be used for up to 3 days before seeking medical advice.

Combining analgesics

When should I combine analgesics?

• In adults:
  • analgesics may be combined if there is a poor response to a full therapeutic dose of an individual analgesic. For example, if the person has an inadequate response to:
    • a full therapeutic dose of paracetamol—consider adding a low dose of ibuprofen (and titrate it up to the full therapeutic dose)
    • a full therapeutic dose of paracetamol and/or a NSAID—consider adding a weak opioid
• In children:
  • administering paracetamol and ibuprofen at the same time is not recommended
  • alternating paracetamol and ibuprofen may be considered only if switching between paracetamol and ibuprofen has been tried, and the distress persists or recurs before the next dose is due
    • for more information, see the section on Which analgesic should I prescribe for children under 16 years of age?

Further information for patients

• The information leaflet Managing your pain effectively using over-the-counter medicines (produced by the British Pain Society) may be useful.