Drugs List

Therapeutic Indications

Uses

Treatment of post-operative pain

Administration

Administer by intramuscular or bolus intravenous injection only.

Bolus intravenous doses should be administered over a minimum of 15 seconds.

Contraindications

Children under 6 months
Haemorrhagic diathesis
Surgery with a risk of incomplete haemostasis
Surgical procedure with high risk of haemorrhage
Suspected cerebrovascular haemorrhage
Acute renal failure
Breastfeeding
Cerebrovascular haemorrhage
Coagulopathy
Dehydration
Gastrointestinal perforation
History of asthma
History of gastrointestinal haemorrhage
History of peptic ulcer
Hypovolaemia
Labour
Nasal polyps, angioedema, and bronchospastic reactivity to NSAIDs
Peptic ulcer
Pregnancy
Renal impairment - serum creatinine above 160 micromol/l
Severe cardiac failure
Severe hepatic impairment

Precautions and Warnings

Children aged 6 months to 16 years
Debilitation
Females attempting to conceive
Patients over 65 years
Predisposition to hypovolaemia
Risk factors for cardiovascular disorder
Weight below 50kg
Cardiac impairment
Cerebrovascular disorder
Congestive cardiac failure
Connective tissue disorder
Crohn's disease
Decompensated cardiac failure
Hepatic impairment
History of bronchospasm
Hypertension
Ischaemic heart disease
Peripheral arterial circulatory disorder
Renal impairment
Systemic lupus erythematosus
Ulcerative colitis

Do not use for prophylactic analgesia prior to surgery
Treatment should be initiated in hospital
Correct volume depletion and monitor patients until normovolaemic
Discontinue if signs of gastro-intestinal bleeding occur
May inhibit platelet aggregation - observe for signs of bleeding
Monitor closely patient with a history of congestive cardiac failure
Monitor patients with pre-existing hypertension
Monitor renal function in patients with renal impairment
Advise patients to report signs or symptoms of gastro-intestinal ulcer
Discontinue if signs of gastro-intestinal ulceration occur
High dose/long term use may increase risk of arterial thrombotic events
May prolong bleeding time
NSAIDs may provoke bronchospasm/urticaria in susceptible patients
NSAIDs may rarely cause interstitial nephritis or glomerulonephritis
NSAIDs may rarely cause renal medullary necrosis or nephrotic syndrome
Risk of gastro-intestinal bleeding increased in the elderly
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if symptoms of hepatic disease occur
Reduce dose and/or alter dose interval in elderly patients
Parenteral use for maximum 2 days
May cause impaired fertility

Ketorolac should not be used for prophylactic analgesia before surgery or for intraoperative analgesia due to the risk of increased bleeding.

Ketorolac should be used with caution in patients with conditions leading to a reduction in blood volume and/or renal blood flow. Administration of NSAIDs in these patients can cause reduced renal prostaglandin formation and may lead to overt renal failure. This effect is more likely in patients who are volume depleted due to blood loss or severe dehydration, patients with renal impairment, cardiac failure and hepatic impairment, the elderly, and those taking diuretics. Patients generally return to their pre-treatment state following discontinuation of NSAIDs.

Patients with systemic lupus erythematosus and mixed connective tissue disorders may have an increased risk of aseptic meningitis.

Pregnancy and Lactation

Pregnancy

Ketorolac is contraindicated in pregnancy. Ketorolac should also be avoided during labour and delivery.

If an NSAID is clinically indicated in the first or second trimester, ibuprofen would be the preferred agent. NSAIDs should be avoided during the third trimester. In circumstances where the clinical condition requires treatment with NSAIDs during the third trimester, the foetus should be monitored regularly for oligohydramnios and to ensure normal circulation. Schaefer concludes that use of a non-preferred agent in early pregnancy (such as ketorolac), does not require termination of pregnancy or invasive diagnostic procedures.

Approximately 10% of the dose crosses the placenta.

There is very limited information concerning ketorolac specifically during pregnancy, however, congenital abnormalities have been reported in association with NSAID administration in humans. However, these are infrequent and do not follow any noticeable pattern. There is an increased risk of spontaneous abortion following maternal exposure to NSAIDs during pregnancy. Ketorolac is a prostaglandin synthesis inhibitor. These inhibitors may expose the foetus to cardiopulmonary toxicity as well as renal dysfunction. The mother and neonate may be exposed to prolongation of bleeding time and/or inhibition of uterine contractions causing a delayed or prolonged labour.

Exposure to NSAIDs after 30 weeks of pregnancy is associated with increased risk of premature closure of the ductus arteriosus and oligohydramnios. The incidence and severity of premature closure of ductus arteriosus appears to be dose related and increases with advancing gestational age beyond 30 weeks.

There was no evidence of teratogenicity in rats or rabbits given maternally toxic doses. A prolonged gestational period and delayed parturition have been observed in rats. Ketorolac and its metabolites transfer into the animal foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Ketorolac is contraindicated in breastfeeding.

UK Drugs in Lactation Advisory Service states that there is no evidence of safety with parenteral use.

Ketorolac and its metabolites have been detected in human milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Abnormal thinking
Acute renal failure
Agranulocytosis
Anaemia
Anaphylaxis
Arterial thrombosis
Aseptic meningitis
Asthenia
Asthma
Bradycardia
Bronchospasm
Cardiac failure
Chest pain
CNS stimulation
Constipation
Convulsions
Dizziness
Dream abnormalities
Drowsiness
Dry mouth
Dyspepsia
Dyspnoea
Epistaxis
Eructation
Exfoliative dermatitis
Fatigue
Fever
Flank pain
Fluid retention
Flushing
Functional disorders
Gastritis
Gastro-intestinal disturbances
Gastro-intestinal pain
Gastro-intestinal ulceration
Gastrointestinal bleeding
Haematemesis
Haematoma
Haematuria
Haemolytic uraemic syndrome
Hallucinations
Headache
Hearing disturbances
Hepatic failure
Hepatitis
Hyperkalaemia
Hyperkinesia
Hypertension
Hyponatraemia
Hypotension
Impaired concentration
Increased thirst
Increased urinary frequency
Infertility
Insomnia
Jaundice
Laryngeal oedema
Local pain (injection site)
Maculopapular rash
Malaise
Melaena
Mood changes e.g. depression, elation
Myalgia
Nephritis
Nephrotic syndrome
Neutropenia
Oedema
Oesophagitis
Oliguria
Pallor
Palpitations
Pancreatitis
Paraesthesia
Peptic ulceration with perforation and haemorrhage
Photosensitivity
Post operative wound haemorrhage
Prolonged bleeding
Pruritus
Psychotic reactions
Pulmonary oedema
Purpura
Rectal bleeding
Serum creatinine increased
Serum urea increased
Stevens-Johnson syndrome
Sweating
Taste disturbances
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Ulcerative stomatitis
Urinary retention
Urticaria
Vertigo
Visual disturbances
Weight gain

Presentation

Injections containing ketorolac

Drugs List

Therapeutic Indications

Uses

Treatment of post-operative pain

Dosage

Dose should be adjusted according to the severity of pain and patient response.

Undesirable effects may be minimised by using the lowest effective dose for the shortest possible duration. Duration of treatment should not exceed 2 days.

Adults

Elderly

Children

Patients with Renal Impairment

Additional Dosage Information

Administration

Administer by intramuscular or bolus intravenous injection only.

Bolus intravenous doses should be administered over a minimum of 15 seconds.

Contraindications

Children under 6 months
Haemorrhagic diathesis
Surgery with a risk of incomplete haemostasis
Surgical procedure with high risk of haemorrhage
Suspected cerebrovascular haemorrhage
Acute renal failure
Breastfeeding
Cerebrovascular haemorrhage
Coagulopathy
Dehydration
Gastrointestinal perforation
History of asthma
History of gastrointestinal haemorrhage
History of peptic ulcer
Hypovolaemia
Labour
Nasal polyps, angioedema, and bronchospastic reactivity to NSAIDs
Peptic ulcer
Pregnancy
Renal impairment - serum creatinine above 160 micromol/l
Severe cardiac failure
Severe hepatic impairment

Precautions and Warnings

Children aged 6 months to 16 years
Debilitation
Females attempting to conceive
Patients over 65 years
Predisposition to hypovolaemia
Risk factors for cardiovascular disorder
Weight below 50kg
Cardiac impairment
Cerebrovascular disorder
Congestive cardiac failure
Connective tissue disorder
Crohn's disease
Decompensated cardiac failure
Hepatic impairment
History of bronchospasm
Hypertension
Ischaemic heart disease
Peripheral arterial circulatory disorder
Renal impairment
Systemic lupus erythematosus
Ulcerative colitis

Do not use for prophylactic analgesia prior to surgery
Treatment should be initiated in hospital
Correct volume depletion and monitor patients until normovolaemic
Discontinue if signs of gastro-intestinal bleeding occur
May inhibit platelet aggregation - observe for signs of bleeding
Monitor closely patient with a history of congestive cardiac failure
Monitor patients with pre-existing hypertension
Monitor renal function in patients with renal impairment
Advise patients to report signs or symptoms of gastro-intestinal ulcer
Discontinue if signs of gastro-intestinal ulceration occur
High dose/long term use may increase risk of arterial thrombotic events
May prolong bleeding time
NSAIDs may provoke bronchospasm/urticaria in susceptible patients
NSAIDs may rarely cause interstitial nephritis or glomerulonephritis
NSAIDs may rarely cause renal medullary necrosis or nephrotic syndrome
Risk of gastro-intestinal bleeding increased in the elderly
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if symptoms of hepatic disease occur
Reduce dose and/or alter dose interval in elderly patients
Parenteral use for maximum 2 days
May cause impaired fertility

Ketorolac should not be used for prophylactic analgesia before surgery or for intraoperative analgesia due to the risk of increased bleeding.

Ketorolac should be used with caution in patients with conditions leading to a reduction in blood volume and/or renal blood flow. Administration of NSAIDs in these patients can cause reduced renal prostaglandin formation and may lead to overt renal failure. This effect is more likely in patients who are volume depleted due to blood loss or severe dehydration, patients with renal impairment, cardiac failure and hepatic impairment, the elderly, and those taking diuretics. Patients generally return to their pre-treatment state following discontinuation of NSAIDs.

Patients with systemic lupus erythematosus and mixed connective tissue disorders may have an increased risk of aseptic meningitis.

Pregnancy and Lactation

Pregnancy

Ketorolac is contraindicated in pregnancy. Ketorolac should also be avoided during labour and delivery.

If an NSAID is clinically indicated in the first or second trimester, ibuprofen would be the preferred agent. NSAIDs should be avoided during the third trimester. In circumstances where the clinical condition requires treatment with NSAIDs during the third trimester, the foetus should be monitored regularly for oligohydramnios and to ensure normal circulation. Schaefer concludes that use of a non-preferred agent in early pregnancy (such as ketorolac), does not require termination of pregnancy or invasive diagnostic procedures.

Approximately 10% of the dose crosses the placenta.

There is very limited information concerning ketorolac specifically during pregnancy, however, congenital abnormalities have been reported in association with NSAID administration in humans. However, these are infrequent and do not follow any noticeable pattern. There is an increased risk of spontaneous abortion following maternal exposure to NSAIDs during pregnancy. Ketorolac is a prostaglandin synthesis inhibitor. These inhibitors may expose the foetus to cardiopulmonary toxicity as well as renal dysfunction. The mother and neonate may be exposed to prolongation of bleeding time and/or inhibition of uterine contractions causing a delayed or prolonged labour.

Exposure to NSAIDs after 30 weeks of pregnancy is associated with increased risk of premature closure of the ductus arteriosus and oligohydramnios. The incidence and severity of premature closure of ductus arteriosus appears to be dose related and increases with advancing gestational age beyond 30 weeks.

There was no evidence of teratogenicity in rats or rabbits given maternally toxic doses. A prolonged gestational period and delayed parturition have been observed in rats. Ketorolac and its metabolites transfer into the animal foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Ketorolac is contraindicated in breastfeeding.

UK Drugs in Lactation Advisory Service states that there is no evidence of safety with parenteral use.

Ketorolac and its metabolites have been detected in human milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Abnormal thinking
Acute renal failure
Agranulocytosis
Anaemia
Anaphylaxis
Arterial thrombosis
Aseptic meningitis
Asthenia
Asthma
Bradycardia
Bronchospasm
Cardiac failure
Chest pain
CNS stimulation
Constipation
Convulsions
Dizziness
Dream abnormalities
Drowsiness
Dry mouth
Dyspepsia
Dyspnoea
Epistaxis
Eructation
Exfoliative dermatitis
Fatigue
Fever
Flank pain
Fluid retention
Flushing
Functional disorders
Gastritis
Gastro-intestinal disturbances
Gastro-intestinal pain
Gastro-intestinal ulceration
Gastrointestinal bleeding
Haematemesis
Haematoma
Haematuria
Haemolytic uraemic syndrome
Hallucinations
Headache
Hearing disturbances
Hepatic failure
Hepatitis
Hyperkalaemia
Hyperkinesia
Hypertension
Hyponatraemia
Hypotension
Impaired concentration
Increased thirst
Increased urinary frequency
Infertility
Insomnia
Jaundice
Laryngeal oedema
Local pain (injection site)
Maculopapular rash
Malaise
Melaena
Mood changes e.g. depression, elation
Myalgia
Nephritis
Nephrotic syndrome
Neutropenia
Oedema
Oesophagitis
Oliguria
Pallor
Palpitations
Pancreatitis
Paraesthesia
Peptic ulceration with perforation and haemorrhage
Photosensitivity
Post operative wound haemorrhage
Prolonged bleeding
Pruritus
Psychotic reactions
Pulmonary oedema
Purpura
Rectal bleeding
Serum creatinine increased
Serum urea increased
Stevens-Johnson syndrome
Sweating
Taste disturbances
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Ulcerative stomatitis
Urinary retention
Urticaria
Vertigo
Visual disturbances
Weight gain

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: July 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Ketorolac 30 mg/ml solution for injection. Beacon Pharmaceuticals. March 2011.

Summary of Product Characteristics: Toradol 30 mg/ml Solution for Injection. Atnahs Pharma UK. Revised September 2015.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 08 September 2017

UK Drugs in Lactation Advisory Service.
Available at: https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Ketorolac. Last accessed: July 21, 2016

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Ketorolac. Last revised: October 22, 2013
Last accessed: July 21, 2016