Subcutaneous NSAIDs in palliative care - ketorolac

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Note: Administration via the subcutaneous route is off-label use.

• Can be used for bone pain in cancer where other analgesics have been ineffective.
• Off-label use when administered via the subcutaneous route.

• Hypersensitivity to aspirin or other NSAIDs, active gastrointestinal (GI) ulceration or active bleeding event

Refer to the British National Formulary (BNF) or Summary of Product Characteristics (SPC) for a full list of contraindications.

Avoid in patients with significant cardiovascular risk factors, for instance cardiac events, myocardial infarction or cardiac failure.

See the BNF for further information.

Liver impairment

The manufacturer cautions use as it may increase the risk of renal impairment. The manufacturer advises avoidance in hepatic failure.

Renal impairment

• Contraindicated in moderate-to-severe renal impairment or in patients at risk of renal failure due to volume depletion or dehydration.
• Avoid if serum creatinine is greater than 160 micromol/L.

Aspirin thromboprophylaxis should be discontinued before use, as ketorolac inhibits platelet aggregation.

Drug interactions

There are several known interactions. Please refer to the BNF or SPC for more information.

• warfarin
• aspirin
• heparin
• other NSAIDs
• pentoxifylline (increased risk of bleeding)
• lithium (increased plasma concentration and toxicity), and
• probenecid (increases ketorolac plasma concentration and half-life).

Cautions with NSAIDs:

• increased risk of renal toxicity with other renally toxic drugs, for example, aminoglycosides, ciclosporin
• increased risk of bleeding as a result of antiplatelet or anticlotting effects, for example, anticoagulants, serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs)
• increased risk of upper gastrointestinal (GI) complications, for example, concurrent prescription of low-dose aspirin, corticosteroids
• antagonistic effect of NSAIDs as a result of sodium and fluid retention, for example, antihypertensives, diuretics, and
• antagonistic effect of some NSAIDs with thromboprophylactic effect of low-dose aspirin.

Monitoring

• Baseline and ongoing monitoring of renal function during use, if appropriate.
• Monitor injection sites as subcutaneous injection can be an irritant.

Side effects

For a full list of side effects, refer to the BNF or SPC. Below are some side effects which are common or significant in palliative care use:

• • headache
  • dyspepsia
  • nausea, abdominal pain
  • abnormal renal function
  • rash, and
  • bleeding and pain at injection site (less with CSCI).

A proton pump inhibitor co-prescription is strongly advised due to the high risk of gastrointestinal ulceration, bleeding or perforation.

For the acute treatment of severe pain

Ketorolac 15–30 mg can be administered by subcutaneous or intramuscular bolus  injection up to three times daily. However, these can be an irritant.

For the prevention and treatment of background pain

Ketorolac can be started at 60 mg over 24 hours, via CSCI, diluted to the largest volume possible of 0.9 % sodium chloride

• DO NOT increase above 60 mg if the patient is less than 50 kg or over 65 years old.
• In patients younger than 65 years old or over 50 kg, this can be increased in 15 mg/24-hour increments to a recommended maximum dose of 90 mg in 24 hours via CSCI.
• During titration, some palliative care specialists may prescribe 15 mg subcutaneous doses as required to be given for breakthrough pain, maximum 3 times in 24 hours. This should not exceed the permitted maximum daily dose taking account of the dose already in the CSCI. However, given the adverse event profile of ketorolac, it is essential that the lowest effective dose is used to minimise the risk of harm.

Discontinuing ketorolac: This may be needed if treatment is ineffective, the patient is experiencing side effects or is experiencing a site reaction.

• Important: ketorolac is alkaline and is given alone via a separate syringe pump because of a lack of information on compatibility with other drugs.
• Always prescribe a proton pump inhibitor for a person receiving ketorolac wherever possible, because of the increased risk of gastrointestinal complications.
• Be aware of the risk of administration error because of unfamiliarity and small dose volumes (of 30 mg/1 mL solution for injection).
• Parecoxib or diclofenac are generally preferred to ketorolac because of their better gastrointestinal and cardiovascular side effect profiles.

Palliative Care Formulary (accessed online): MedicinesComplete - CONTENT > Palliative Care Formulary > Drug: *Ketorolac trometamol (accessed 21/04/2025)

Ketorolac SPC (accessed online): Ketorolac Trometamol 30 mg/mL solution for injection - Summary of Product Characteristics (SmPC) - (emc) | 11547 (accessed 21/04/2025)

Ketorolac BNF (accessed online): Ketorolac trometamol | Drugs | BNF | NICE (accessed 21/04/2025)

Association of Paediatric Palliative Medicine (downloaded online): APPM formulary 6th edition 2024 Final 2023-10-26.pdf(accessed 21/04/2025)