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TORADOL 30 MG/ML SOLUTION FOR INJECTION

Active substance(s): KETOROLAC TROMETAMOL / KETOROLAC TROMETAMOL / KETOROLAC TROMETAMOL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Toradol 30 mg/ml Solution for Injection

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Toradol contains ketorolac trometamol 30mg in ampoules of 1ml. It also contains
ethanol, sodium chloride and water.

3

PHARMACEUTICAL FORM
Toradol is a clear, slightly yellow solution for intramuscular or bolus intravenous
injection.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Toradol is indicated for the short-term management of moderate to severe acute postoperative pain.
Treatment should only be initiated in hospitals. The maximum duration of treatment
is two days.

4.2

Posology and method of administration
Toradol is for administration by intramuscular or bolus intravenous injection.
Bolus intravenous doses should be given over no less than 15 seconds.
Toradol should not be used for epidural or spinal administration.
The time to onset of analgesic effect following both IV and IM administration
is similar and is approximately 30 minutes, with maximum analgesia occurring
within one to two hours. The median duration of analgesia is generally four to
six hours.
Dosage should be adjusted according to the severity of the pain and the patient
response.

The administration of continuous multiple daily doses of ketorolac
intramuscularly or intravenously should not exceed two days because adverse
events may increase with prolonged usage. There has been limited experience
with dosing for longer periods since the vast majority of patients have
transferred to oral medication, or no longer require analgesic therapy after this
time.
Undesirable effects may be minimised by using the lowest effective dose for
the shortest duration necessary to control symptoms (see section 4.4).
Adults
The recommended initial dose of Toradol is 10 mg, followed by 10 to 30 mg
every four to six hours as required. In the initial post-operative period,
Toradol may be given as often as every two hours if needed. The lowest
effective dose should be given. A total daily dose of 90 mg for non-elderly
and 60 mg for the elderly, renally-impaired patients and patients less than 50
kg should not be exceeded. The maximum duration of treatment should not
exceed two days.
Reduce dosage in patients under 50 kg.
Opioid analgesics (e.g. morphine, pethidine) may be used concomitantly, and
may be required for optimal analgesic effect in the early post-operative period
when pain is most severe. Ketorolac does not interfere with opioid binding and
does not exacerbate opioid-related respiratory depression or sedation. When
used in association with Toradol IM/IV, the daily dose of opioid is usually less
than that normally required. However, opioid side-effects should still be
considered, especially in day-case surgery.
Elderly
The elderly are at increased risk of the serious consequences of adverse
reactions. If an NSAID is considered necessary, the lowest effective dose
should be used and for the shortest possible duration. The patient should be
monitored regularly for GI bleeding during NSAID therapy. A total daily dose
of 60 mg should not be exceeded (see section 4.4).
Children
Safety and efficacy in children have not been established. Therefore, Toradol
is not recommended for use in children under 16 years of age.
Renal impairment
Contraindicated in moderate to severe renal impairment; reduce dosage in
lesser impairment (not exceeding 60 mg/day IV or IM) (see section 4.3).

4.3

Contraindications
Ketorolac is contraindicated in patients with previously demonstrated hypersensitivity
to Ketorolac, any of its excipients, or other NSAIDs and patients in whom aspirin or
other prostaglandin synthesis inhibitors induce allergic reactions (severe

anaphylactic-like reactions have been observed in such patients). Such reactions have
included asthma, rhinitis, angioedema, or urticaria.
Ketorolac is also contraindicated in
- those with a history of asthma
- children under 16 years of age.
Ketorolac is contraindicated in patients with active peptic ulcer, or any history of
gastrointestinal bleeding, ulceration or perforation.
As with other NSAIDs, Ketorolac is contraindicated in patients with severe heart
failure, hepatic failure and renal failure (see section 4.4).
Ketorolac is contraindicated in patients with moderate or severe renal impairment
(serum creatinine >160 µmol/l) or in patients at risk for renal failure due to volume
depletion or dehydration.
Ketorolac is contraindicated in pregnancy, labour, delivery or lactation (see section
4.6).
Ketorolac is contraindicated as prophylactic analgesia before surgery due to inhibition
of platelet aggregation and is contra-indicated intra-operatively because of the
increased risk of bleeding.
Ketorolac inhibits platelet function and is, therefore, contraindicated in patients with
suspected or confirmed cerebrovascular bleeding, patients who have had operations
with a high risk of haemorrhage or incomplete haemostasis and those at high risk of
bleeding such as those with haemorrhagic diatheses, including coagulation disorders.
It is also contraindicated in patients on anticoagulants, including warfarin and low
dose heparin (2500 - 5000 units 12 hourly).
Ketorolac is contraindicated in patients currently receiving ASA or other NSAIDs
(including cyclooxygenase-2 selective inhibitors).
Ketorolac Solution for injection is contraindicated for neuraxial (epidural or
intrathecal) administration due to its alcohol content.
The combination of Ketorolac with oxpentifylline is contraindicated.
Concurrent treatment with ketorolac and probenecid or lithium salts is
contraindicated.
Ketorolac is contraindicated in patients with the complete or partial syndrome of
nasal polyps, angioedema or bronchospasm.

4.4

Special warnings and precautions for use
Ketorolac: Epidemiological evidence suggests that ketorolac may be
associated with a high risk of serious gastrointestinal toxicity, relative to
some other NSAIDs, especially when used outside the licensed indications
and/ or for prolonged periods (see also section 4.1, 4.2 and 4.3).
Physicians should be aware that in some patients pain relief may not occur
until upwards of 30 minutes after IV or IM administration.
The use of ketorolac with concomitant NSAIDs including cyclooxygenase-2
selective inhibitors should be avoided.

Undesirable effects may be minimised by using the minimum effective dose
for the shortest duration necessary to control symptoms (see section 4.2 and GI
and cardiovascular risks below).
Gastrointestinal ulceration, bleeding and perforation
GI bleeding, ulceration or perforation, which can be fatal, has been reported
with all NSAIDs including ketorolac therapy, at anytime during treatment,
with or without warning symptoms or a previous history of serious GI events.
In a non-randomised, in-hospital post-marketing surveillance study, increased
rates of clinically serious GI bleeding were seen in patients < 65 years of age
who received an average daily dose of > 90 mg ketorolac IM as compared to
those patients receiving parenteral opioids.
The elderly have an increased frequency of adverse reactions to NSAIDs,
especially gastrointestinal bleeding and perforation which may be fatal (see
section 4.2).
The risk of GI bleeding, ulceration or perforation is higher with increasing
NSAID doses, including ketorolac IV, in patients with a history of ulcer,
particularly if complicated with haemorrhage or perforation (see section 4.3),
and in the elderly. The risk of clinically serious gastrointestinal bleeding is
dose dependent. These patients should commence treatment on the lowest dose
available. Combination therapy with protective agents (e.g. misoprostol or
proton pump inhibitors) should be considered for these patients, and also for
patients requiring concomitant low dose aspirin, or other drugs likely to
increase gastrointestinal risk (see below and section 4.5). This age-related risk
of gastrointestinal bleeding and perforation is common to all NSAIDs.
Compared to young adults, the elderly have an increased plasma half-life and
reduced plasma clearance of ketorolac. A longer dosing interval is advisable
(see section 4.2).
NSAIDs should be given with care to patients with a history of inflammatory
bowel disease, (ulcerative colitis, Crohn’s disease) as these conditions may be
exacerbated (see section 4.8). Patients with a history of GI toxicity,
particularly when elderly, should report any unusual abdominal symptoms
(especially GI bleeding) particularly in the initial stages of treatment. When GI
bleeding or ulceration occurs in patients receiving ketorolac IV, treatment
should be withdrawn.
Caution should be advised in patients receiving concomitant medications
which could increase the risk of ulceration or bleeding, such as oral
corticosteroids, selective serotonin-reuptake inhibitors or anti-platelet agents
such as aspirin (see section 4.5).
Use in patients taking anti-coagulants such as warfarin is contraindicated (see
section 4.3).
As with other NSAIDs the incidence and severity of gastrointestinal
complications may increase with increasing dose and duration of treatment

with ketorolac IV. The risk of clinically serious gastrointestinal bleeding is
dose-dependent. This is particularly true in elderly patients who receive an
average daily dose greater than 60 mg/day of ketorolac IV. A history of peptic
ulcer disease increases the possibility of developing serious gastrointestinal
complications during ketorolac therapy.
Haematological effects
Patients with coagulation disorders should not receive Toradol. Patients on
anti-coagulation therapy may be at increased risk of bleeding if given Toradol
concurrently. The concomitant use of ketorolac and prophylactic low dose
heparin (2500 - 5000 units 12-hourly) and dextrans has not been studied
extensively and may also be associated with an increased risk of bleeding.
Patients already on anti-coagulants or who require low-dose heparin should
not receive ketorolac. Patients who are receiving other drug therapy that
interferes with haemostasis should be carefully observed if Toradol is
administered. In controlled clinical studies, the incidence of clinically
significant postoperative bleeding was less than 1%.
Ketorolac inhibits platelet aggregation and prolongs bleeding time. In patients
with normal bleeding function, bleeding times were raised, but not outside the
normal range of two to eleven minutes. Unlike the prolonged effects from
aspirin, platelet function returns to normal within 24 to 48 hours after
ketorolac is discontinued.
In post-marketing experience, postoperative wound haemorrhage has been
reported in association with the peri-operative use of Toradol IM/IV.
Therefore, ketorolac should not be used in patients who have had operations
with a high risk of haemorrhage or incomplete haemostasis. Caution should be
used where strict haemostasis is critical, e.g. in cosmetic or day-case surgery,
resection of the prostate or tonsillectomy. Haematomas and other signs of
wound haemorrhage and epistaxis have been reported with the use of Toradol.
Physicians should be aware of the pharmacological similarity of ketorolac to
other non-steroidal anti-inflammatory drugs that inhibit cyclooxygenase and
the risk of bleeding, particularly in the elderly.
Skin reactions
Serious skin reactions, some of them fatal, including exfoliative dermatitis,
Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported
very rarely in association with the use of NSAIDs (see section 4.8). Patients
appear to be at highest risk for these reactions early in the course of therapy:
the onset of the reactions occurring in the majority of cases within the first
month of treatment. Toradol should be discontinued at the first appearance of
skin rash, mucosal lesions or any other sign of hypersensitivity.
SLE and mixed connective tissue disease
In patients with systemic lupus erythematosus (SLE) and mixed connective
tissue disorders there may be an increased risk of aseptic meningitis (see
section 4.8).
Sodium/fluid retention in cardiovascular conditions and peripheral oedema

Caution is required in patients with a history of hypertension and /or heart
failure as fluid retention and oedema have been reported in association with
NSAID therapy.
Fluid retention, hypertension and peripheral oedema has been observed in
some patients taking NSAIDs including ketorolac and it should therefore be
used with caution in patients with cardiac decompensation, hypertension or
similar conditions.
Cardiovascular and cerebrovascular effects
Appropriate monitoring and advice are required for patients with a history of
hypertension and/or mild to moderate congestive heart failure as fluid
retention and oedema have been reported in association with NSAID therapy.
Clinical trial and epidemiological data suggest that use of coxibs and some
NSAIDs (particularly at high doses) may be associated with a small increased
risk of arterial thrombotic events (for example myocardial infarction or
stroke). Although ketorolac has not been shown to increase thrombotic events
such as myocardial infarction, there are insufficient data to exclude such a risk
for ketorolac.
Patients with uncontrolled hypertension, congestive heart failure, established
ischaemic heart disease, peripheral arterial disease and/or cerebrovascular
disease should only be treated with ketorolac after careful consideration.
Similar consideration should be made before initiating treatment of patients
with risk factors for cardiovascular disease (e.g. hypertension,
hyperlipidaemia, diabetes mellitus and smoking).
Cardiovascular, Renal and Hepatic Impairment
Caution should be observed in patients with conditions leading to a reduction
in blood volume and/or renal blood flow, where renal prostaglandins have a
supportive role in the maintenance of renal perfusion. In these patients,
administration of an NSAID may cause a dose-dependent reduction in renal
prostaglandin formation and may precipitate overt renal failure. Patients at
greatest risk of this reaction are those who are volume depleted because of
blood loss or severe dehydration, patients with impaired renal function, heart
failure, liver dysfunction, the elderly and those taking diuretics. Renal function
should be monitored in these patients. Discontinuation of NSAID therapy is
typically followed by recovery to the pre-treatment state. Inadequate
fluid/blood replacement during surgery, leading to hypovolaemia, may lead to
renal dysfunction which could be exacerbated when Toradol is administered.
Therefore, volume depletion should be corrected and close monitoring of
serum urea and creatinine and urine output is recommended until the patient is
normovolaemic. In patients on renal dialysis, ketorolac clearance was reduced
to approximately half the normal rate and terminal half-life increased
approximately three-fold (see section 4.3).
Renal effects
As with other NSAIDs ketorolac should be used with caution in patients with
impaired renal function or a history of kidney disease because it is a potent

inhibitor of prostaglandin synthesis. Caution should be observed as renal
toxicity has been seen with ketorolac and other NSAIDs in patients with
conditions leading to a reduction in blood volume and/or renal blood flow
where renal prostaglandins have a supportive role in the maintenance of renal
perfusion.
In these patients administration of ketorolac or other NSAIDs may cause a
dose-dependent reduction in renal prostaglandin formation and may precipitate
overt renal decompensation or failure. Patients at greatest risk of this reaction
are those with impaired renal function, hypovolaemia, heart failure, liver
dysfunction, those taking diuretics and the elderly. Discontinuation of
ketorolac or other non-steroidal anti-inflammatory therapy is usually followed
by recovery to the pre-treatment state.
As with other drugs that inhibit prostaglandin synthesis, elevations of serum
urea, creatinine and potassium have been reported with ketorolac trometamol
and may occur after one dose.
Patients with impaired renal function: Since ketorolac trometamol and its
metabolites are excreted primarily by the kidney, patients with moderate to
severe impairment of renal function (serum creatinine greater than 160
micromol/l) should not receive Toradol. Patients with lesser renal impairment
should receive a reduced dose of ketorolac (not exceeding 60 mg/day IM or
IV) and their renal status should be closely monitored.
Use in patients with impaired liver function: Patients with impaired hepatic
function from cirrhosis do not have any clinically important changes in
ketorolac clearance or terminal half-life.
Borderline elevations of one or more liver function tests may occur. These
abnormalities may be transient, may remain unchanged, or may progress with
continued therapy. Meaningful elevations (greater than 3 times normal) of
serum glutamate pyruvate transaminase (SGPT/ALT) or serum glutamate
oxaloacetate transaminase (SGOT/AST) occurred in controlled clinical trials
in less than 1% of patients. If clinical signs and symptoms consistent with liver
disease develop, or if systemic manifestations occur, Toradol should be
discontinued.
Anaphylactic (anaphylactoid) reactions
Anaphylactic (anaphylactoid) reactions (including, but not limited to,
anaphylaxis, bronchospasm, flushing, rash, hypotension, laryngeal oedema
and angioedema) may occur in patients with or without a history of
hypersensitivity to aspirin, other NSAIDs or ketorolac IV. These may also
occur in individuals with a history of angioedema, bronchospastic reactivity
(e.g. asthma) and nasal polyps. Anaphylactoid reactions, like anaphylaxis, may
have a fatal outcome. Therefore, ketorolac should not be used in patients with
a history of asthma and in patients with the complete or partial syndrome of
nasal polyps, angioedema and bronchospasm (see section 4.3).
Precautions related to fertility

The use of Toradol, as with any drug known to inhibit
cyclooxygenase/prostaglandin synthesis, may impair fertility and is not
recommended in women attempting to conceive. In women who have
difficulty conceiving or are undergoing investigation of fertility, withdrawal of
Toradol should be considered.
Fluid retention and oedema
Fluid retention, hypertension and oedema have been reported with the use of
ketorolac and it should therefore be used with caution in patients with cardiac
decompensation, hypertension or similar conditions.
Caution is advised when methotrexate is administered concurrently since some
prostaglandin synthesis-inhibiting drugs have been reported to reduce the
clearance of methotrexate, and thus possibly enhance its toxicity.
Drug Abuse and Dependence
Ketorolac is devoid of addictive potential. No withdrawal symptoms have
been observed following abrupt discontinuation of ketorolac IV.

4.5

Interaction with other medicinal products and other forms of interaction
Ketorolac is highly bound to human plasma protein (mean 99.2%) and binding
is concentration-independent.
The following medicinal products are NOT to be co-administered with
Toradol:
Toradol should not be used with other ASA or other NSAIDs including
cyclooxygenase-2 selective inhibitors as the risk of inducing serious NSAIDrelated adverse events may be increased (see section 4.3).
Ketorolac inhibits platelet aggregation, reduces thromboxane concentrations
and prolongs bleeding time. Unlike the prolonged effects from aspirin, platelet
function returns to normal within 24-48 hours after ketorolac is discontinued.
Toradol is contraindicated in combination with anti-coagulants, such as
warfarin since co-administration of NSAIDs and anti-coagulants may cause an
enhanced anti-coagulant effect (see section 4.3).
Although studies do not indicate a significant interaction between ketorolac
and warfarin or heparin the concurrent use of ketorolac and therapy that
affects haemostasis, including therapeutic doses of anti-coagulation therapy
(warfarin) prophylactic low-dose heparin (2500-5000 units 12-hourly) and
dextrans may be associated with an increased risk of bleeding.
Inhibition of renal lithium clearance, leading to an increase in plasma lithium
concentration, has been reported with some prostaglandin synthesis-inhibiting
drugs. Cases of increased lithium plasma concentrations during ketorolac
therapy have been reported.

Probenecid should not be administered concurrently with ketorolac because of
increases in ketorolac plasma concentrations and half-life.
NSAIDs should not be used for eight to twelve days after mifepristone
administration as NSAIDs can reduce the effects of mifepristone.
When ketorolac is administered concurrently with oxpentifylline, there is an
increased tendency to bleeding.
The following medicinal products in combination with Toradol, are to be coadministered with caution:
As with all NSAIDs, caution should be taken when co-administering with
corticosteroids because of the increased risk of gastrointestinal ulceration or
bleeding (see section 4.4).
There is an increased risk of gastrointestinal bleeding (see section 4.4) when
anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs) are
combined with NSAIDs.
Some prostaglandin synthesis-inhibiting drugs have been reported to reduce
the clearance of methotrexate, and thus possibly enhance its toxicity.
Ketorolac tromethamine does not alter digoxin protein binding. In vitro
studies indicated that at therapeutic concentrations of salicylate (300µg/ml),
the binding of ketorolac was reduced from approximately 99.2% to 97.5%
representing a potential twofold increase in unbound ketorolac plasma
concentrations. Therapeutic concentrations of digoxin, warfarin, ibuprofen,
naproxen, piroxicam, acetaminophen, phenytoin and tolbutamide did not alter
ketorolac protein binding.
Ketorolac Solution for injection reduced the diuretic response to furosemide in
normovolemic healthy subjects by approximately 20% so particular care
should be taken in patients with cardiac decompensation.
Co-administration with diuretics can lead to a reduced diuretic effect, and
increase the risk of nephrotoxicity of NSAIDs.
As with all NSAIDs caution is advised when ciclosporin is co-administered
because of the increased risk of nephrotoxicity.
There is a possible risk of nephrotoxicity when NSAIDs are given with
tacrolimus.
NSAIDs may reduce the effect of diuretics and anti-hypertensive medicinal
products. The risk of acute renal insufficiency, which is usually reversible,
may be increased in some patients with compromised renal function (e.g.
dehydrated patients or elderly patients) when ACE inhibitors and/or
angiotensin II receptor antagonists are combined with NSAIDs. Therefore, the

combination should be administered with caution, especially in the elderly.
Patients should be adequately titrated and consideration should be given to
monitoring renal function after initiation of concomitant therapy, and
periodically thereafter.
NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma
cardiac glycoside levels when co-administered with cardiac glycosides.
Ketorolac has been shown to reduce the need for concomitant opioid analgesia
when it is given for the relief of postoperative pain.
Animal data indicate that NSAIDs can increase the risk of convulsions
associated with quinolone antibiotics. Patients taking NSAIDs and quinolones
may have an increased risk of developing convulsions.
NSAIDs given with zidovudine increase the risk of haematological toxicity.
There is evidence of an increased risk of haemarthroses and haematoma in
HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and
ibuprofen.
There is no evidence in animal or human studies that ketorolac trometamol
induces or inhibits the hepatic enzymes capable of metabolising itself or other
drugs. Hence Toradol would not be expected to alter the pharmacokinetics of
other drugs due to enzyme induction or inhibition mechanisms.

4.6

Fertility, Pregnancy and lactation
In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of
closure of the ductus arteriosus) ketorolac is contraindicated during pregnancy, labour
or delivery.
The safety of Toradol during human pregnancy has not been established. There was
no evidence of teratogenicity in rats or rabbits studied at maternally-toxic doses of
ketorolac. Prolongation of the gestation period and/or delayed parturition were seen in
the rat. Congenital abnormalities have been reported in association with NSAID
administration in man, however these are low in frequency and do not follow any
discernible pattern. In view of the known effects of NSAIDs on the foetal
cardiovascular system (risk of closure of the ductus arteriosus) ketorolac is
contraindicated during pregnancy, labour or delivery.
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the
embryo/foetal development. Data from epidemiological studies suggest an increased
risk of miscarriage and of cardiac malformation and gastroschisis after use of a
prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for
cardiovascular malformation was increased from less than 1%, up to approximately
1.5 %. The risk is believed to increase with dose and duration of therapy. In animals,
administration of a prostaglandin synthesis inhibitor has been shown to result in
increased pre- and post-implantation loss and embryo-foetal lethality. In addition,
increased incidences of various malformations, including cardiovascular, have been

reported in animals given a prostaglandin synthesis inhibitor during the organogenetic
period.
During pregnancy, all prostaglandin synthesis inhibitors may expose
the foetus to:
cardiopulmonary toxicity (with premature closure of the ductus arteriosus and
pulmonary hypertension);
renal dysfunction, which may progress to renal failure with oligohydroamniosis;
the mother and the neonate, at the end of pregnancy, to:
possible prolongation of bleeding time, an anti-aggregating effect which may
occur even at very low doses.
-

inhibition of uterine contractions resulting in delayed or prolonged labour.

See section 4.4 regarding female fertility.
Ketorolac crosses the placenta to the extent of approximately 10%.
Labour and Delivery
Ketorolac is contraindicated in labour and delivery because, through its prostaglandin
synthesis inhibitory effect it may adversely affect foetal circulation and inhibit uterine
contractions, thus increasing the risk of uterine haemorrhage.
There may be increased bleeding tendency in both mother and child (see section 4.3)
Nursing Mothers
Ketorolac and its metabolites have been shown to pass into the foetus and milk of
animals. Ketorolac has been detected in human milk at low concentrations, therefore
ketorolac is contraindicated in mothers who are breast-feeding.

4.7

Effects on ability to drive and use machines
Some patients may experience dizziness, drowsiness, fatigue, visual disturbances,
headaches, vertigo, insomnia or depression with the use of Toradol. If patients
experience these, or other similar undesirable effects, patients should not drive or
operate machinery.

4.8

Undesirable effects
Post Marketing

The following undesirable effects may occur in patients receiving ketorolac
IV; frequencies of reported events are not known, because they were reported
voluntarily from a population of uncertain size.
Gastro-intestinal Disorders: The most commonly observed adverse events
are gastrointestinal in nature. Peptic ulcers, ulcers, perforation or GI bleeding,
sometimes fatal, particularly in the elderly, may occur (see section 4.4).
Nausea, vomiting, diarrhoea, constipation, dyspepsia, abdominal pain /
discomfort, melaena, haematemesis, stomatitis, ulcerative stomatitis,
eructation, flatulence, oesophagitis, gastrointestinal ulceration, rectal bleeding,
pancreatitis, dry mouth, fullness, exacerbation of colitis and Crohn’s disease
(see section 4.4) have been reported following administration. Less frequently,
gastritis has been observed.
Infection: meningitis aseptic. (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus, mixed connective
tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting,
fever or disorientation (see section 4.4).
Blood and Lymphatic System Disorders: thrombocytopenia
Additionally purpura, neutropenia, agranulocytosis, aplastic anaemia and
haemolytic anaemia have been observed.
Immune System Disorders: anaphylaxis, anaphylactoid reactions,
anaphylactoid reactions like anaphylaxis, may have a fatal outcome,
hypersensitivity reactions such as bronchospasm flushing, rash, hypotension,
laryngeal oedema.
These may also occur in individuals with a history of angioedema,
bronchospastic reactivity (e.g. asthma and nasal polyps).
Metabolic and Nutrition Disorders: anorexia, hyperkalaemia, hyponatraemia.
Psychiatric Disorders: abnormal thinking, depression, insomnia, anxiety,
nervousness, psychotic reactions, abnormal dreams, hallucinations, euphoria,
concentration ability impaired, drowsiness.
Confusion and stimulation have been observed.
Nervous System Disorders: headache, dizziness, convulsions, paresthesia,
hyperkinesias, taste abnormality.
Eye Disorders: abnormal vision, visual disturbances, optic neuritis.
Ear Disorders: tinnitus, hearing loss, vertigo.
Renal and Urinary Disorders: acute renal failure, increased urinary
frequency, interstitial nephritis, nephrotic syndrome, urinary retention,
oliguria, haemolytic uremic syndrome, flank pain (with or without haematuria

+- azotemia). As with other drugs that inhibit renal prostaglandin synthesis,
signs of renal impairment, such as, but not limited to elevations of creatinine
and potassium can occur after one dose of Ketorolac IV.
Cardiac Disorders: palpitations, bradycardia, cardiac failure.
Vascular Disorders: hypertension, hypotension, haematoma, flushing, pallor,
postoperative wound haemorrhage.
Clinical trial and epidemiological data suggest that use of coxibs and some
NSAIDs (particularly at high doses) may be associated with a small increased
risk of arterial thrombotic events (for example myocardial infarction or
stroke). Although ketorolac has not shown to increase thrombotic events, such
as myocardial infarction, there are insufficient data to exclude such a risk with
ketorolac.
Reproductive System and Breast Disorders: female infertility.
Respiratory, Thoracic and Mediastinal Disorders: asthma, dyspnoea,
pulmonary oedema. Additionally epistaxis has been observed.
Hepatobiliary Disorders: hepatitis, cholestatic jaundice, liver failure.
Skin and Subcutaneous Tissue Disorders: exfoliative dermatitis,
maculopapular rash, pruritus, urticaria, purpura, angioedema, sweating,
bullous reactions including Stevens-Johnson syndrome and toxic epidermal
necrolysis (very rare).
Additionally erythema multiforme and skin photosensitivity has been
observed.
Musculoskeletal and Connective Tissue Disorders: myalgia, functional
disorder.
General Disorders and Administration Site Condition: excessive thirst,
asthenia, oedema, injection site reactions and pain, fever, chest pain.
Additionally, malaise, fatigue and weight gain has been observed.
Investigations: bleeding time prolonged, serum urea increased, creatinine
increased, abnormal liver function tests.
Laboratory Abnormalities
See Section Post Marketing (Undesirable Effects).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance
of the medicinal product. Healthcare professionals are asked to report any

suspected adverse reactions via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.

4.9

Overdose
Symptoms and signs
Single overdoses of Ketorolac have been variously associated with abdominal
pain, nausea, vomiting, hyperventilation, peptic ulcers and/or erosive gastritis
and renal dysfunction which have resolved after discontinuation of dosing.
Gastrointestinal bleeding may occur. Hypertension, acute renal failure,
respiratory depression and coma may occur after the ingestion of NSAIDs but
are rare.
Headache, epigastric pain, disorientation, excitation, drowsiness, dizziness,
tinnitus and fainting have also been observed.
Rare cases of diarrhoea and occasional convulsions have been reported.
Anaphylactoid reactions have been reported with therapeutic ingestion of
NSAIDs and may occur following an overdose.
Treatment:
Patients should be managed by symptomatic and supportive care following
NSAIDs overdose. There are no specific antidotes. Dialysis does not
significantly clear ketorolac from the blood stream.
Within one hour of ingestion of a potentially toxic amount, activated charcoal
should be considered. Alternatively, in adults, gastric lavage should be
considered within one hour of ingestion of a potentially life-threatening
overdose.
Good urine output should be ensured. Renal and liver function should be
closely monitored. Patients should be observed for at least four hours after
ingestion of potentially toxic amounts. Frequent or prolonged convulsions
should be treated with intravenous diazepam. Other measures may be
indicated by the patient’s clinical condition.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Toradol is a potent analgesic agent of the non-steroidal, anti-inflammatory class
(NSAID). It is not an opioid and has no known effects on opioid receptors. Its mode
of action is to inhibit the cyclo-oxygenase enzyme system and hence prostaglandin

synthesis, and it demonstrates a minimal anti-inflammatory effect at its analgesic
dose.

5.2

Pharmacokinetic properties
IM: Following intramuscular administration, ketorolac trometamol was
rapidly and completely absorbed, a mean peak plasma concentration of
2.2mcg/ml occurring an average of 50 minutes after a single 30mg dose. The
influences of age, kidney and liver function on terminal plasma half-life and
mean total clearance are outlined in the table below (estimated from a single
30mg IM dose of ketorolac).
Type of subjects

Normal subjects (n = 54)
Patients with hepatic dysfunction
(n
= 7)
Patients with renal impairment (n
=
25) (serum creatinine 160 - 430
micromol/l)
Renal dialysis patients (n = 9)
Healthy elderly subjects (n = 13)
(mean age 72)

Total clearance
(l/hr/kg) mean
(range)
0.023 (0.010 0.046)
0.029 (0.013 -

Terminal half-life
(hrs) mean (range)
5.3 (3.5 - 9.2)
5.4 (2.2 - 6.9)

0.066)
0.016 (0.005 -

10.3 (5.9 - 19.2)

0.043)
0.016 (0.003 0.036)
0.019 (0.013 0.034)

13.6 (8.0 - 39.1)
7.0 (4.7 - 8.6)

IV: Intravenous administration of a single 10mg dose of ketorolac trometamol
resulted in a mean peak plasma concentration of 2.4mcg/ml occurring an
average of 5.4 minutes after dosing, with a terminal plasma elimination halflife of 5.1 hours, an average volume of distribution of 0.15 l/kg, and a total
plasma clearance of 0.35ml/min/kg.
The pharmacokinetics of ketorolac in man following single or multiple doses
are linear. Steady-state plasma levels are achieved after dosing every 6 hours
for one day. No changes in clearance occurred with chronic dosing. The
primary route of excretion of ketorolac and its metabolites is renal: 91.4%
(mean) of a given dose being found in the urine and 6.1% (mean) in the
faeces.
More than 99% of the ketorolac in plasma is protein-bound over a wide
concentration range.

5.3

Preclinical safety data
An 18-month study in mice with oral doses of ketorolac trometamol at 2mg/kg/day
(0.9 times human systemic exposure at the recommended IM or IV dose of 30mg qid,
based on area-under-the-plasma-concentration curve [AUC]), and a 24-month study
in rats at 5mg/kg/day (0.5 times the human AUC), showed no evidence of
tumorigenicity.
Ketorolac trometamol was not mutagenic in the Ames test, unscheduled DNA
synthesis and repair, and in forward mutation assays. Ketorolac trometamol did not
cause chromosome breakage in the in vivo mouse micronucleus assay. At
1590mcg/ml and at higher concentrations, ketorolac trometamol increased the
incidence of chromosomal aberrations in Chinese hamster ovarian cells.
Impairment of fertility did not occur in male or female rats at oral doses of 9mg/kg
(0.9 times the human AUC) and 16mg/kg (1.6 times the human AUC) of ketorolac
trometamol, respectively.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Ethanol
Sodium Chloride
Water

6.2

Incompatibilities
Toradol should not be mixed in a small volume (e.g. in a syringe) with
morphine sulfate, pethidine hydrochloride, promethazine hydrochloride or
hydroxyzine hydrochloride as precipitation of ketorolac will occur.
It is compatible with normal saline, 5% dextrose, Ringer's, lactated Ringer's or
Plasmalyte solutions. Compatibility of Toradol with other drugs is unknown.

6.3

Shelf life
3 years.

6.4

Special precautions for storage
Keep the ampoules in the outer carton. Do not refrigerate or freeze. Do not use if
particulate matter is present.

6.5

Nature and contents of container
Toradol 30mg is available in single-dose ampoules containing 1ml of solution in
cartons of 1, 5 or 10.

6.6

Special precautions for disposal
No special instructions applicable.

7

MARKETING AUTHORISATION HOLDER
Atnahs Pharma UK Limited
Sovereign House
Miles Gray Road
Basildon
Essex
SS14 3FR
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 43252/0009

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
31 May 1996

10

DATE OF REVISION OF THE TEXT
11/09/2015

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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