Ketorolac

Ketorolac is a pyrrolo-pyrrole NSAID with potent analgesic and weak anti-inflammatory activity, used short term for moderate to severe acute pain. Parenteral doses of 10 to 30 mg give analgesia comparable to opioid doses in many postoperative and renal colic settings.

Class. Nonselective NSAID.

Mechanism. Inhibition of COX-1 and COX-2. The S-enantiomer carries analgesic activity.

Pharmacokinetics. Oral bioavailability about 80 to 100%. Intravenous onset about 30 minutes, peak 1 to 2 hours, duration 4 to 6 hours. Protein binding about 99%. Half-life about 5 hours; 6 to 7 hours in older adults and 9 hours or longer in renal impairment. Eliminated mainly by the kidney (about 90%).

Indications are short-term (maximum 5 days) management of moderate to severe acute pain, including postoperative pain, renal colic and musculoskeletal injury. Not for chronic pain or minor pain.

Adults under 65 years, 50 kg or more, normal renal function

• Single dose: 30 mg intravenous or 60 mg intramuscular.
• Repeated doses: 30 mg intravenous or intramuscular every 6 hours. Maximum 120 mg in 24 hours.
• Oral continuation (only after parenteral dosing): 20 mg first dose then 10 mg every 4 to 6 hours. Maximum 40 mg in 24 hours.

Age 65 or over, weight under 50 kg, or kidney impairment

• Single dose: 15 mg intravenous or 30 mg intramuscular.
• Repeated doses: 15 mg every 6 hours. Maximum 60 mg in 24 hours.
• Oral continuation: 10 mg every 4 to 6 hours. Maximum 40 mg in 24 hours.

Duration. Total of all routes combined must not exceed 5 days. In some regions the parenteral limit is 2 days with a lower daily ceiling (10 mg first, then 10 to 30 mg every 4 to 6 hours, maximum 90 mg in 24 hours, or 60 mg in older adults); follow the local label.

Dose-response. Evidence suggests a ceiling effect near 10 mg intravenously for many patients; the lowest effective dose is advised. This is contested.

Children 2 to 16 years. Single dose only: 0.5 mg/kg intravenously (maximum 15 mg) or 1 mg/kg intramuscularly (maximum 30 mg). Repeated paediatric dosing is specialist practice.

Loading dose, titration. Not applicable beyond the reduced first dose for older or lighter patients.

Contraindications. Active peptic ulcer or recent gastrointestinal bleeding or perforation; suspected or confirmed cerebrovascular bleeding; bleeding diathesis or high risk of bleeding; advanced renal impairment or risk of renal failure from hypovolaemia; concurrent aspirin, other NSAIDs, probenecid or pentoxifylline; labour and delivery; breastfeeding; pregnancy; prophylactic use before major surgery; around coronary artery bypass surgery; hypersensitivity to NSAIDs; intrathecal or epidural administration.

Boxed-warning-level risks. Gastrointestinal bleeding and perforation; acute kidney injury; bleeding from platelet inhibition (also postoperative bleeding); arterial thrombotic events; anaphylactoid reactions; risk to the foetus and labour; dose-related risk when the daily dose or duration is exceeded.

Adverse effects. Common: nausea, dyspepsia, abdominal pain, headache, dizziness, drowsiness, injection-site pain. Serious: gastrointestinal haemorrhage, acute kidney injury, hyperkalaemia, wound haematoma and surgical-site bleeding, bronchospasm, anaphylaxis and severe skin reactions.

Interactions. Contraindicated with aspirin, other NSAIDs, probenecid and pentoxifylline. Additive bleeding with anticoagulants, antiplatelets, SSRIs and corticosteroids. Kidney injury with ACE inhibitors, angiotensin receptor blockers, diuretics, ciclosporin and tacrolimus. Raised lithium and methotrexate. Seizure risk with quinolones and with antiepileptics.

Common prescribing errors. Exceeding 5 days; omitting the reduced dose in older adults, in patients under 50 kg or in renal impairment; combining with another NSAID; using the intramuscular dose for intravenous administration; giving before surgery with bleeding risk; giving to a hypovolaemic patient before fluid resuscitation.

Special groups

• Pregnancy: contraindicated (and avoid at any gestation if a safer analgesic is available).
• Breastfeeding: contraindicated.
• Children: single-dose use only, outside specialist practice.
• Older adults: use the reduced doses.
• Kidney impairment: use the reduced dose with caution in mild to moderate; avoid if advanced.
• Liver impairment: caution; avoid with severe disease.
• Regional: availability varies, so check which strength and diluent are stocked. Avoid in suspected dengue or other haemorrhagic fever.

Formulations. Injection 10, 15, 30 and 60 mg/mL; tablets 10 mg.

Administration. Intravenous bolus over at least 15 seconds. Intramuscular injection is given slowly and deeply. Never give by the intrathecal or epidural route. Keep oral doses short and only as continuation.

Baseline. Blood volume status, creatinine and eGFR, weight, age, coagulation status, ulcer history, pregnancy status and concurrent medicines.

Monitoring. Urine output and creatinine in patients with risk factors. Signs of bleeding (wound, gastrointestinal, urinary). Blood pressure. Haemoglobin if bleeding is suspected. Count days of total exposure on the chart.

Therapeutic drug monitoring. Not used.

Stopping thresholds. Stop at 5 days (or the local limit), or earlier for bleeding, creatinine rise of 30% or more, oliguria, gastrointestinal symptoms or hypersensitivity.

Referral and escalation. Bleeding, anuria, anaphylaxis or severe hypertension needs urgent assessment. Pain not controlled by ketorolac within 1 to 2 hours warrants senior review and an opioid or regional technique.